Pitavastatin Promotes Heart Health in HIV Patients by Stabilizing Atherosclerotic Plaques, New Study Finds

 Your competent? doctor should look at this and determine if any of their patients have unstable plaque that caused the stroke, well maybe this should be administered. Don't listen to me, I'm not medically trained. Is your doctor?

Pitavastatin Promotes Heart Health in HIV Patients by Stabilizing Atherosclerotic Plaques, New Study Finds

Can't copy, so read at link.

16.5M Americans at risk of stroke from exercising too hard: study

The stroke isn't caused by blocked carotid arteries, it's caused by rupturing the plaque and sending clots to your brain. So you need to know the stability of your plaque. 

This might be the answer: calcified plaque

A better way to predict heart attacks and strokes in space  August 2018

What is your doctor doing to clear that plaque?  Stenting doesn't clear anything.

Do you want the lawnmower?
Lawnmower For Clogged Arteries
Or Drano? I would be worried about this, sloughing off chunks
Drano For Clogged Arteries
Or conventional?
9 Complications With Coronary Artery Bypass Surgery

Or this?

Israeli study uses gold particles to ‘seek and destroy’ artery blockages

But I'd rather my doctor told me how much watermelon juice to drink.

Watermelon juice reverses hardening of the arteries  Nov. 2011

I'm not medically trained so nothing here should be brought to your doctor's attention because they being completely up-to-date will already know about it.

The latest here:

16.5M Americans at risk of stroke from exercising too hard: study

Push it — but not too hard.

Nearly 16.5 million Americans are at risk of stroke from exercising too hard, a new study found.

Published in the scientific journal Physics of Fluid, researchers concluded that an elevated heart rate can induce a stroke in those with blocked carotid arteries.

Carotid arteries are located on both sides of the neck and provide blood flow to the face and the brain.

But when fat and cholesterol build up, they form a plaque that narrows the artery, a process called stenosis. Stenosis can be very difficult to detect early on and is dangerous because it limits blood flow to the brain, which can lead to a stroke.

An estimated 16.5 million (5%) Americans are estimated to experience carotid artery stenosis, according to the Cleveland Clinic.

Those who smoke, are obese, live a sedentary lifestyle and have high blood pressure, high cholesterol or diabetes are more likely to suffer from carotid artery stenosis. It can also develop with age.

A recent study found that the 16.5 million Americans who suffer from carotid artery stenosis are at risk of stroke from exercising too hard.

Getty Images

Researchers from the Indian Institute of Technology Kharagpur concluded that an elevated heart rate can induce a stroke in those with blocked carotid arteries.

Getty Images/iStockphoto

Researchers from the Indian Institute of Technology Kharagpur used a computational model to simulate blood flow in carotid arteries at three stages of stenosis: without blockage, with a mild 30% blockage and with a moderate 50% blockage.

They compared the effect of an exercise-induced heart rate at 140 beats per minute, which can be achieved by a brisk walk for some obese people, and resting heart rates of 67 and 100 bpm.

Healthy patients and those with only slightly blocked arteries appeared to have exercise be beneficial for maintaining healthy blood flow.

However, the results for those with moderate to severe blockage were concerning.

“Intense exercise shows adverse effects on patients with moderate or higher stenosis levels,” said author Somnath Roy.

“It substantially increases the shear stress at the stenosis zone, which may cause the stenosis to rupture. This ruptured plaque may then flow to the brain and its blood supply, causing ischemic stroke.”

The researchers concluded that “while stressful exercises may be beneficial for improving the cardiac performance of healthy individuals, the same may bring in extremely adverse consequences … for patients having extensive arterial blockages.”

Getty Images

Carotid Atherosclerotic Calcification Characteristics Relate to Post-stroke Cognitive Impairment

My doctors never found the 80% blockage in my right carotid artery, which thankfully completely closed up in three years.  I think my post stroke cognitive impairment is zilch.

Carotid Atherosclerotic Calcification Characteristics Relate to Post-stroke Cognitive Impairment

 

Yingzhe Wang^1†, Chanchan Li^2†, Mengyuan Ding¹, Luyi Lin², Peixi Li¹, Yizhe Wang³, Qiang Dong^1,4, Yanmei Yang^2*‡ and Mei Cui^1,4*‡

• ¹Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
• ²Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
• ³Department of Medicine, Nanchang University, Nanchang, China
• ⁴The State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

Background: Together with cerebral small vessel disease (CSVD), large vessel atherosclerosis is considered to be an equally important risk factor in the progression of vascular cognitive impairment. This article aims to investigate whether carotid atherosclerotic calcification is associated with the increased risk of post-stroke cognitive impairment (PSCI).

Methods: A total of 128 patients (mean age: 62.1 ± 12.2 years, 37 women) suffering from ischemic stroke underwent brain/neck computer tomography angiography examination. The presence and characteristic of carotid calcification (size, number and location) were analyzed on computer tomography angiography. White matter hyperintensity (WMH) was assessed using Fazekas scales. PSCI was diagnosed based on a battery of neuropsychological assessments implemented 6−12 months after stroke.

Results: Among 128 patients, 26 developed post-stroke dementia and 96 had carotid calcification. Logistic regression found carotid calcification (odds ratio [OR] = 7.15, 95% confidence interval [CI]: 1.07–47.69) and carotid artery stenosis (OR = 6.42, 95% CI: 1.03–40.15) both significantly increased the risk for post-stroke dementia. Moreover, multiple, thick/mixed, and surface calcifications exhibited an increasing trend in PSCI (P_trend = 0.004, 0.016, 0.045, respectively). The prediction model for post-stroke dementia including carotid calcification (area under curve = 0.67), WMH (area under curve = 0.67) and other covariates yielded an area under curve (AUC) of 0.90 (95% CI: 0.82–0.99).

Conclusion: Our findings demonstrated that the quantity and location of carotid calcifications were independent indicators for PSCI. The significant role of large vessel atherosclerosis in PSCI should be concerned in future study.

Introduction

Stroke is considered to be one of the most widespread and serious cerebrovascular diseases affecting millions of people worldwide. With a high prevalence of 20–80%, post-stroke cognitive impairment (PSCI) is one of the major complications suffered during the chronic stage of ischemic stroke (Sun et al., 2014). As cognitive function can fluctuate due to neurological deficits and subsequent improvement of perfusion in early phases, the diagnosis of PSCI is often postponed by at least 3 months after the onset of stroke (Gottesman and Hillis, 2010). Thus, early identification of patients at high-risk of PSCI, based on patients’ baseline characteristics, is essential in the orchestration of appropriate preventataive management.

Several factors, including age, education level, vascular risk factors, extent of stroke, and neuroimaging features, are considered to be important determinants of PSCI (Rasquin et al., 2004; Leys et al., 2005; Lu et al., 2016). Apart from acute stroke, pre-existing cerebral small vessel disease (CSVD) is believed to be closely connected with both the prognosis of stroke and the occurrence of cognitive dysfunction. It has been reported that PSCI was significantly associated with several subtypes of baseline CSVD, including white matter hyperintensity (WMH), cerebral microbleed, enlarged perivascular space and brain atrophy (Wen et al., 2004; Gregoire et al., 2012; Kebets et al., 2015; Molad et al., 2017; Arba et al., 2018). Interestingly, although CSVD is often accompanied by pathological changes in large arteries, the relationship between large vessel diseases (such as stenosis, slow blood flow, malformation, or poor collateral circulation) and PSCI remains ambiguous. While some research has demonstrated that large vessel stenosis was highly predictive of PSCI (Kandiah et al., 2016; Li et al., 2017), not all studies have shown consistent results (Chaudhari et al., 2014). Understanding the relationship between atherosclerotic calcification and PSCI will provide a deeper insight into the pathology of PSCI, which would be beneficial for early diagnosis and prevention.

Therefore, in this study, we aimed to investigate whether the presence of carotid atherosclerotic calcification is an associated risk factor for the development and progression of PSCI, and whether this association depends on the characteristic of calcification.

More at link,

Atherosclerotic Plaque Disruption and Healing

If it ever occurs the final result of this research should provide interventions that make sure your plaque is the extinct version. What is your stroke hospital doing to ensure this research is followed up and creates protocols?

Atherosclerotic Plaque Disruption and Healing

As with geologists, cardiovascular researchers have long studied the mechanisms governing atherosclerotic plaque formation, disruption, and thrombosis (i.e. the ‘volcanoes’ eruption’), and the ascertained knowledge has guided our traditional approaches to atherosclerosis therapy. Yet the ability to predict plaque instability and the development of acute coronary syndrome (ACS) or sudden coronary death remains weak, suggesting that other potential pathogenic mechanisms should also be explored.²

In our review article recently published in the New England Journal of Medicine,³ we explored the hidden side of the moon: mechanisms of atherosclerotic plaque healing and their clinical and potential therapeutic implications. We know from historical pathology studies that healed plaques can be frequently found at the non-culprit coronary sites of patients dying from sudden cardiac death, and even in subjects dying from other causes.⁴ These plaques can be considered as ‘inactive volcanoes’ within the vasculature, either ‘extinct’ or ‘dormant’. By definition, an ‘extinct volcano’ is a volcano that has not erupted for at least 10 000 years and is not supposed to erupt again in the future, while a ‘dormant’ one is a volcano that is not erupting, but is expected to erupt again.¹

As with volcanoes, the healing process can either pacify the disrupted plaque so that it remains silent for the rest of the patient’s life, or instead, stabilize it for a variable time period before a new disruption occurs. Both pathology and in vivo imaging studies in fact suggest that atherosclerotic plaques may undergo multiple episodes of disruption and healing, and that accumulation of new granulation tissue may contribute to an increase in plaque burden and to progressive luminal narrowing.^4,5

Recent optical coherence tomography studies showed an association between the presence of healed coronary plaques and higher non-target lesion, ischaemia-driven revascularization rates, in the absence of acute events.⁶ These data confirm our original observation that patients with healed plaques are more likely to evolve towards a long-standing chronic coronary syndrome (CCS), while those without evidence of healed plaques more frequently experience a recurrence of ACS.⁵ These observations have led us to propose the ‘double hit’ theory of atherosclerosis as a possible explanation of the pathogenesis of ACS.^3,5,7 This is somewhat reminiscent of what happened in oncology where, after studying oncogenes for decades, it was discovered that half of all human cancers were prompted by a mutation in oncogene suppressor genes. In atherosclerosis, the first hit is the acute destabilization of an atherosclerotic plaque by either rupture or erosion, whereas the second hit is an impaired healing capacity.³

Why are these findings important for patients with ischaemic heart disease? Because they may help to better predict the natural history of coronary atherosclerosis and, most importantly, they may pave the way towards novel therapeutic strategies. While traditional therapies have focused almost exclusively on preventing atherosclerosis progression and on treating its acute thrombotic complications, new therapies may point strongly towards strategies of improving healing. Patients with an effective healing capacity seem to have more potent endogenous fibrinolytic and thrombolytic systems as well as polarization of inflammation towards a reparative phenotype, including the production of anti-inflammatory cytokines and the overexpression of alternative M2 macrophages.³

Therapeutic options might come from existing drugs as well as from novel agents. Intensive antithrombotic therapy has already proved effective in promoting healing of coronary plaque erosion,⁸ and the beneficial effects of aggressive lipid-lowering agents (e.g. high-dose statins, proprotein convertase subtilisin–kexin type 9 inhibitors) on plaque stabilization have been largely documented.³

Promising results may come from the use of anti-inflammatory agents, such as interleukin-1β antagonists (e.g. canakinumab) or low-dose colchicine.^9,10 Recently, low-dose colchicine has been demonstrated to significantly lower the risk of cardiovascular events in a randomized trial involving patients with CCS compared to placebo.¹⁰ Although the mechanisms behind this benefit have not been elucidated, they may be at least in part related to an improvement in a plaque healing capacity. Another intriguing approach may be the modulation of macrophage polarization towards a reparative phenotype through CD31-targeting molecules or epigenetic therapies, including DNA methylation, histone modifications, or modulation of microRNAs and long non-coding RNAs.³

In conclusion, although primary prevention and traditional therapies provide a key to stemming the worldwide spread of the atherosclerotic disease epidemic and its thrombotic complications, the recognition of the healing process as an active player, rather than an innocent bystander, in the pathogenesis of ischaemic heart disease may provide ground for novel treatment options. We must strive to move beyond the classic approach of focusing on the mechanisms of plaque instability only, and try to elucidate the hidden protective mechanisms, with the aim of converting ‘poor healers’ into ‘good healers’.

During the Second World War, Sir Winston Churchill stated: ‘Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning’. In the current era, we might be at the same turning point in the war against atherosclerosis. Promoting plaque healing in addition to preventing plaque disruption might considerably potentiate our armamentarium in the battle against cardiovascular diseases.

 

Atherosclerosis Progresses Rapidly in Healthy People From the Age of 40

At age 50 despite being extremely healthy my right carotid artery got to 80% closure, which is not a problem except that the plaque tore, clotted and sent that clot to the brain. I would never have stented that because the risk from stenting is too great and ideally my doctors would have tested for a complete Circle of Willis.  For 10 years that artery was completely closed which was great, now I guess collaterals have formed around it.  My coronary arteries are pretty good though.  What is your doctor doing to clear that plaque?  Stenting doesn't clear anything.

Do you want the lawnmower?
Lawnmower For Clogged Arteries
Or Drano? I would be worried about this, sloughing off chunks
Drano For Clogged Arteries
Or conventional?
9 Complications With Coronary Artery Bypass Surgery

Or this?

Israeli study uses gold particles to ‘seek and destroy’ artery blockages

But I'd rather my doctor told me how much watermelon juice to drink.

Watermelon juice reverses hardening of the arteries  Nov. 2011

I'm not medically trained so nothing here should be brought to your doctor's attention because they being completely up-to-date will already know about it.

The latest here:

Atherosclerosis Progresses Rapidly in Healthy People From the Age of 40

Atheroma plaques extend rapidly through the arteries of 40% of asymptomatic individuals aged 40 to 50 years, according to a study published in the Journal of American College of Cardiology.

“The key finding of the study is that over a short follow-up of just 3 years, 40% of individuals aged 40 to 50 years showed major progression of atherosclerosis in distinct locations, including the carotid, femoral, and coronary arteries,” said Beatriz López-Melgar, MD, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. “This rapid disease progression could make these individuals more vulnerable to developing symptoms or having clinical events such as a myocardial infarction or stroke.”

The Progression of Early Subclinical Atherosclerosis (PESA) study has been monitoring 4,200 healthy middle-aged men and women with noninvasive imaging technology, such as 2D or 3D ultrasound, for more than 10 years.

“[Noninvasive technology] allows us to identify the progression of the disease earlier than is possible with classical markers, such as the presence of coronary calcium detected by computed tomography, thus allowing us to identify individuals at higher risk who could benefit from early intervention,” said Valentín Fuster, MD, CNIC.

“This study is the first to analyse the progression of atherosclerosis at frequent intervals,” added Borja Ibañez, MD, CNIC. “The previous view was that the disease progressed very slowly throughout life. However, the new results show that the disease progressed very rapidly in 40% of the individuals analysed.”

The researchers conclude that the findings, while they await validation from the occurrence of events in the PESA cohort in the future, will be of great value for the identification of strategies to stall the epidemic of cardiovascular disease.

“Future data from the PESA study will show whether this progression is associated with subsequent cardiovascular events,” said Dr. Ibañez. “Until now, the speed of atherosclerosis progression has not been a factor in assessing individual risk.”

Reference: http://www.onlinejacc.org/content/75/14/1617

SOURCE: Centro Nacional de Investigaciones Cardiovasculares Carlos III

Anti-JNK2 peptide–siRNA nanostructures improve plaque endothelium and reduce thrombotic risk in atherosclerotic mice

Well, human followup needed but will never occur since we have complete fucking failures of stroke associations, NO stroke leadership and NO stroke strategy. Stroke is obviously not important to anyone in charge.
Way back in Feb. 2013 this same conclusion was written up,  inhibiting the enzyme JNK protected reperfusion injury in rats. WHOSE INCOMPETENCE needs to be called out for not doing one damn thing with this old research? There is one hell of a lot of incompetence in stroke that needs to be removed. There are NO excuses that can condone this behavior.

Compound Developed by Scripps Florida Scientists Protects Heart Cells During and After Attack  Feb. 2013

Anti-JNK2 peptide–siRNA nanostructures improve plaque endothelium and reduce thrombotic risk in atherosclerotic mice

Authors Pan H, Palekar RU, Hou KK, Bacon J, Yan H, Springer LE, Akk A, Yang L, Miller MJ, Pham CTN, Schlesinger PH, Wickline SA
Received 18 March 2018
Accepted for publication 15 June 2018
Published 6 September 2018 Volume 2018:13 Pages 5187—5205
DOI https://doi.org/10.2147/IJN.S168556
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Thomas J Webster

Hua Pan,¹ Rohun U Palekar,² Kirk K Hou,³ John Bacon,² Huimin Yan,³ Luke E Springer,³ Antonina Akk,³ Lihua Yang,³ Mark J Miller,³ Christine TN Pham,³ Paul H Schlesinger,³ Samuel A Wickline<sup>1

1</sup>Department of Cardiovascular Sciences, USF Health, Morsani College of Medicine, The USF Health Heart Institute, University of South Florida, Tampa, FL, USA; ²Department of Medicine, Washington University, St Louis, MO, USA; ³Department of Biomedical Engineering, Washington University, St Louis, MO, USA

Background: A direct and independent role of inflammation in atherothrombosis was recently highlighted by the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial, showing the benefit of inhibiting signaling molecules, eg, interleukins. Accordingly, we sought to devise a flexible platform for preventing the inflammatory drivers at their source to preserve plaque endothelium and mitigate procoagulant risk.
Methods: p5RHH-siRNA nanoparticles were formulated through self-assembly processes. The therapeutic efficacy of p5RHH-JNK2 siRNA nanoparticles was evaluated both in vitro and in vivo.
Results: Because JNK2 is critical to macrophage uptake of oxidized lipids through scavenger receptors that engender expression of myriad inflammatory molecules, we designed an RNA-silencing approach based on peptide–siRNA nanoparticles (p5RHH-siRNA) that localize to atherosclerotic plaques exhibiting disrupted endothelial barriers to achieve control of JNK2 expression by macrophages. After seven doses of p5RHH-JNK2 siRNA nanoparticles over 3.5 weeks in ApoE^-/- mice on a Western diet, both JNK2 mRNA and protein levels were significantly decreased by 26% (P=0.044) and 42% (P=0.042), respectively. Plaque-macrophage populations were markedly depleted and NFκB and STAT3-signaling pathways inhibited by 47% (P<0.001) and 46% (P=0.004), respectively. Endothelial barrier integrity was restored (2.6-fold reduced permeability to circulating 200 nm nanoparticles in vivo, P=0.003) and thrombotic risk attenuated (200% increased clotting times to carotid artery injury, P=0.02), despite blood-cholesterol levels persistently exceeding 1,000 mg/dL. No adaptive or innate immunoresponses toward the nanoparticles were observed, and blood tests after the completion of treatment confirmed the largely nontoxic nature of this approach.
Conclusion: The ability to formulate these nanostructures rapidly and easily interchange or multiplex their oligonucleotide content represents a promising approach for controlling deleterious signaling events locally in advanced atherosclerosis.

Green Tea Molecule Could Prevent Stroke

Some of my positive posts here:

Green Tea Boosts Your Brain

Green Tea Or Coffee May Reduce Stroke Risk

Green Tea Boosts Memory

 

Be very careful with green tea extract:

Herbal supplements linked to at least six Australian organ transplants since 2011, data shows  March 2016

Green Tea Molecule Could Prevent Stroke

Posted by Lynn Bronikowski Jul 11 2018

 

Sipping a cup of green tea is not only relaxing but scientists are now discovering it could hold the key to preventing strokes and heart attacks.

Green tea, say the scientists from Lancaster University and the University of Leeds, contains a compound that breaks up and dissolves potentially dangerous protein plaques found in the blood vessels that could cause stroke.

Researchers found that antioxidants—most commonly associated with green tea—bind to the amyloid fibers of a protein called apoA-1. This converts the fibers to smaller soluble molecules that are less likely to be damaging to blood vessels.

Now, the team is working on finding ways of introducing effective amounts of antioxidants into the bloodstream without it being necessary to drink large and potentially harmful quantities of green tea.

"The health benefits of green tea have been widely promoted,” said David Middleton, professor in chemistry at Lancaster University. "Our results show that this intriguing compound might also be effective against the types of plaques which can cause heart attacks and strokes."

Added professor Sheena Radford, director of the Astbury Centre for Structural Molecular Biology at the University of Leeds and co-author of the research, "The findings of this round of studies are very encouraging. We now need to apply the best scientific techniques to find how we can take the molecular EGCG (epigallocatechin gallate) element from green tea, and turn it into a functioning tool to combat life-limiting health issues."

The research was funded by the British Heart Foundation and published in the Journal of Biological Chemistry.

Like this article? Donate now to keep StrokeSmart free to anyone that needs it.

Study examines the rise of plaque in arteries

Maybe we could finally address the root cause of atherosclerosis rather than taking statins to lower cholesterol levels. But statins are a cash cow for Big Pharma, they won't go lightly even with overwhelming evidence.  Probably won't occur in my lifetime.
https://medicalxpress.com/news/2018-05-plaque-arteries.html

The accumulation of cholesterol plaques in artery walls can lead to atherosclerosis, or the hardening of arteries that contributes to heart attacks and strokes. In a new study, Yale researchers investigate how plaque cells develop at the molecular level, and their findings could help produce targeted treatments for the disease.

Smooth muscle cells, the dominant type of cell found in artery walls, are known to be involved in plaque build-up, but it has not been clear how this occurs. The research team, led by senior study author Daniel Greif, used mice models and primary human cells to study smooth muscle cells and their contribution to atherosclerotic plaques.

They discovered that a single smooth muscle cell gives rise, through a process of clonal expansion, to the majority of cells found in the plaque. Additionally, they learned that a gene known as integrin beta3 regulates the migration of a single smooth muscle cell progenitor from the artery wall into plaque. Once inside the plaque, the progenitor cell reproduces and changes into other cell types. Further, the researchers determined that the gene's role in plaque development occurs in smooth muscle cells as well as in bone marrow-derived cells.   

Together, the findings shed light on the complex mechanisms behind the progression of atherosclerosis, and suggests potential targets for future therapies, the researchers note.

The study is published in Nature Communications.

Nanoparticle Atherosclerosis Tx Promising in Early Study

Did your doctors know about this study before you told them?
https://www.medpagetoday.com/cardiology/atherosclerosis/72866?

Injecting targeted nanofibers reduced atherosclerotic plaques

• by Nicole Lou, Contributing Writer, MedPage Today May 14, 2018
• This article is a collaboration between MedPage Today® and:
  

A novel nanofiber approach targeting atherosclerosis may rapidly reduce plaque burden, a mouse study suggested.
At 8 weeks of treatment with the nanofiber incorporating a liver X receptor agonist, plaques were 11% and 9% smaller by area in male and female mice, respectively, reported Neel Mansukhani, MD, of Northwestern University in Chicago, in a poster at the American Heart Association's Vascular Discovery: From Genes to Medicine Scientific Sessions in San Francisco.
Mansukhani and colleagues said this shows that their novel approach is specific to atherosclerotic lesions and reduces plaque burden after a short time.
"This therapy is designed to be injected systemically but to target and exert its effects only at areas of atherosclerosis. This allows for lower effective doses of therapeutic agents which may otherwise be toxic at higher doses required for efficacy with systemic administration," he told MedPage Today.
The researchers fed these LDL receptor-knockout mice a high-fat diet for 14 weeks and subsequently gave the animals biweekly injections of self-assembling peptide amphiphile nanofibers or control for 8 weeks. At an optimum concentration of 2 mg/mL, the nanofiber could be targeted to atherosclerotic plaque in the aortic root, localizing there for 2 to 3 days before clearing out during days 7 to 10.
Nicholas Leeper, MD, of Stanford University, California, also said that the specificity of these nanoparticles made the study "very exciting."
"The field of nanotherapies has recently expanded beyond its origins as a platform for cancer theranostics into the cardiovascular realm. Work in this area promises to allow precision treatment of atherosclerosis, which remains the leading cause of death in the United States," commented Leeper, who was not part of the study.
Nanofiber therapy for atherosclerosis still needs further study in animal models before moving onto humans, Mansukhani cautioned, adding that next steps include accurately classifying how the liver X receptor agonist is released from the nanofiber and investigating other potential therapeutic agents.

The study was funded by grants from the National Heart, Lung, and Blood Institute of the NIH and the American Medical Association Foundation.
Mansukhani and Leeper disclosed no relevant conflicts of interest.

• Primary Source

  American Heart Association's Vascular Discovery: From Genes to Medicine Scientific Sessions 2018

  Source Reference: Mansukhani NA, et al "Targeted nanotherapy for the treatment of atherosclerosis" AHA 2018.

Mechanism shown to reverse disease in arteries

This would seem to make much more sense than treating for cholesterol.
https://medicalxpress.com/news/2017-06-mechanism-shown-reverse-disease-arteries.html
A certain immune reaction is the key, not to slowing atherosclerosis like cholesterol-lowering drugs do, but instead to reversing a disease that gradually blocks arteries to cause heart attacks and strokes.

This is the finding of a study in mice led by researchers at NYU Langone Medical Center and published online June 26 in the Journal of Clinical Investigation.
The study focuses on reversing the effects of "bad cholesterol," which is deposited into the walls lining blood vessels in levels influenced by both genetics and a person's diet. By the fourth decade of life, and thanks to the chronic reaction to cholesterol, most people have inflamed "wounds" in their arteries called plaques, which when severe enough can rupture to cause blood clots that block arteries.
"Even the latest, most potent cholesterol-lowering drugs, PCSK9 inhibitors, let alone widely used statins, cannot fully reverse damage done to arteries over time, and so they can't prevent roughly 500,000 heart attacks per year in the United States," says lead study author Edward Fisher, MD, PhD, director of the Marc and Ruti Bell Vascular Biology and Disease Program at NYU Langone.
"We need the next generation of drugs to go beyond cholesterol lowering to address the immune reaction to accumulated cholesterol, and to dismantle plaques as part of reversing or regressing mature disease," says Fisher, the Leon H. Charney Professor of Cardiovascular Medicine at NYU Langone.
In years of painstaking research, the NYU Langone-led research team has zeroed in on the molecular events that occur in arteries when regression of atherosclerotic plaques is underway.
Once deposited into arteries, bad cholesterol - known to physicians as low density lipoprotein - triggers the body's immune system, which is meant to destroy invading microbes but can drive inflammatory disease in the wrong context. Immune cells in the bloodstream called monocytes swarm to cholesterol deposits, and become either inflammatory or healing cell types based on signals there.

In situations where disease is worsening in a plaque, past studies have shown that monocytes become M1 macrophages that amplify immune responses, increase inflammation, and secrete enzymes that gnaw at plaques until they rupture. The current study confirmed that monocytes arriving in plaques where disease is regressing instead become M2 "healing" macrophages, which dampen inflammation and prevent the ruptures that precede clotting.
When mice were engineered to lose the ability of monocytes to become M2 macrophages, they could no longer achieve normal disease regression, say the authors.
By surgically transplanting plaques from diseased mice into the arteries of healthy mice, the research team brought about dramatic drops in cholesterol levels. This drop has been shown to trigger a second benefit in mice, where monocytes automatically become M2 instead of M1 macrophages as plaques rapidly regress.
It is not known whether cholesterol lowering alone triggers this M2 switch in humans. But new imaging techniques may soon be able to detect changes in the type and number of macrophages in plaques. In the meantime, if researchers learn how to boost the M2 switch, a number of clinical applications may become possible just as methods arrive that can measure their success.
"A race is underway to develop treatments that enhance the decision of human monocytes to become M2 macrophages in cases where the disease has not yet caused clot formation, at which point it becomes irreversible," says Fisher.
Specifically, the current study found that the same blood-borne Ly6Chigh monocytes, once thought of only as precursors to "inflammation-prone" M1 macrophages, instead become anti-inflammatory M2 cells when they arrive in a regressing plaque. Having found the class of cells from which M2 macrophages arise, the team is now seeking to identify the local signals that tell monocytes to become M2.
Among the candidates are the immune signaling proteins interleukin-4 and interleukin-13, which have been linked by past studies to the M2 decision. These interleukins are known to turn on the STAT6 pathway, which sends this protein to the nucleus where it turns on genes that direct a monocyte to become a M2 macrophage. Researchers confirmed that blocking the action of STAT6 reduced the number of M2 macrophages in regressing plaques.
Fisher's team is already experimenting with nanoparticles based on the structure of "good cholesterol," which is known to take cholesterol of out of plaques and deliver it to the liver for destruction. One version of their nanoparticle delivers interleukin 4 to plaques as well. A next step for the work would be a study of nanoparticles in pigs, a model where success can set the stage for human trials.

Explore further: Macrophage proliferation appears to drive progression of atherosclerosis

microRNA reduces stroke risk

So this could have probably prevented my carotid plaque from tearing. That would have meant that I wouldn't be having the time of my life here in Michigan.

Why my stroke was the best thing to ever happen to me

The latest here:

microRNA reduces stroke risk

02 May 2017 Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

The molecule microRNA-210 stabilises deposits in the carotid artery and can thus prevent them from tearing, and prevent dangerous blood clots from forming. This is what scientists headed by Prof. Lars Mägdefessel, Professor of Vascular Biology at the Technical University of Munich (TUM) and head of a junior scientist group in the German Centre for Cardiovascular Research (DZHK) have discovered. Their results open up new treatment approaches to reduce stroke risk in patients with carotid arteries at risk of rupturing.
The most common cause for the narrowing of the carotid artery and thus the major risk factor for strokes is atherosclerosis, where so-called plaques build up on the vessel walls. If a plaque ruptures, blood clots can form that either further occlude the site that is already narrowed, or are carried away by the blood flow, which could lead to vascular occlusion at a different site. If this happens in the carotid artery, it could lead to a stroke. How easily a plaque ruptures depends on how thick the tissue layer surrounding its core is. The thicker this so-called fibrous cap, the more stable and thus more harmless the vessel deposit.
New trend: Stabilising instead of reducing
“New imaging procedures enable us to detect dangerous plaques with increasing precision; but the therapies currently available for removing these unstable plaques and thus preventing a stroke entail a certain amount of risk that the plaques will rupture during the procedure”, explains Mägdefessel. “This is why these therapies are not used on individuals with a narrowed carotid artery who have so far not experienced any symptoms.” In an experimental manner, microRNA-210 provides the opportunity to alleviate such dangerous, unstable plaques. It stabilises the fibrous cap so that it cannot rupture as easily. “Traditionally, physicians try to reduce the size of the deposits in the vessels in order to widen the narrowed sites. Yet for narrowed carotid arteries, the notion of stabilising the plaques is becoming ever more prevalent. Unlike in the coronary vessels, in the carotid artery plaques rupturing is more dangerous than the narrowing.”
Tiny regulators
Mägdefessel and his team compared material from patients with stable and unstable deposits in the carotid artery. They particularly focused on microRNAs. These molecules are involved in the gene regulation in about 60 percent of mammals’ genes. They can prevent gene information that has already been read from being translated into proteins, and have become a focus of biomedical research as active ingredients and starting points for new therapies in recent years.
Mägdefessel and his team discovered that microRNA-210 was reduced the most in the blood samples of patients with unstable plaques. These were blood samples that were obtained locally near the vessel deposits. Further examinations showed that microRNA-210 is primarily present in the fibrous caps of plaques and that it inhibits the expression of the APC gene. As a consequence, fewer smooth muscle cells die in the fibrous cap and it becomes more stable. Moreover, the animal model could show that fewer plaques rupture when microRNA-210 is additionally administered.
Local application is crucial
The scientists are currently researching how microRNA-210 can be applied locally. The risk of adverse events in other organs is much too high if microRNA modulators are administered systemically. In particular, the main concern with microRNA-210 is that tumour cells that are possibly already in existence will multiply, because the expression of APC is inhibited. This is because APC is a tumour suppressor gene which inhibits the growth of tumours in the healthy body. In order to avoid such so-called off-target effects, the researchers are currently testing coated stents or balloons that are inserted directly into the carotid artery in pigs. “For this step, we also rely on the collaboration with companies that, for example, develop soft balloons that cause little friction and thus make the procedure safer”, says Mägdefessel. “Only thus will our results reach patients as effective therapies.”

• Full bibliographic informationOriginal study:
  
  MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions.
  
  Eken SM, Jin H, Chernogubova E, Li Y, Simon N, Sun C, Korzunowicz G, Busch A, Bäcklund A, Österholm C, Razuvaev A, Renné T, Eckstein HH, Pelisek J, Eriksson P, González Díez M, Perisic Matic L, Schellinger IN, Raaz U, Leeper NJ, Hansson GK, Paulsson-Berne G, Hedin U, Maegdefessel L.
  
  Circ Res. 2017 Feb 17;120(4):633-644.
  
  DOI: 10.1161/CIRCRESAHA.116.309318
  
  http://circres.ahajournals.org/content/120/4/633

Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right

I can see no use for this knowledge, even as it is an interesting factoid. My right carotid artery dissected, left one was clear.

Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right

The authors compared atherosclerotic plaque prevalence, severity, and composition between left and right carotid arteries. Carotid atherosclerotic plaque size and composition are not symmetrically distributed. Predominance of intraplaque hemorrhage in left–sided carotid plaques suggests a greater vulnerability as opposed to right–sided plaques, which are more calcified and therefore considered more stable.

Go to PubMed Go to Abstract Print Article Summary Cat 2 CME Report

Two new studies explore the science of cardiovascular diseases

Interesting possibility.
http://medicalxpress.com/news/2016-09-explore-science-cardiovascular-diseases.html
Professor of cardiology Martin A. Schwartz led two recently published studies that advance knowledge of the underlying biology of cardiovascular diseases, which are among the most common causes of chronic illness and death worldwide. The studies highlight how basic science research insights are key to future breakthroughs in treatment.

The first study, published in Nature Cell Biology, examined the process that leads to formation of the atherosclerotic plaques that clog arteries and cause heart attacks and strokes. Atherosclerosis research and therapies have focused mainly on lipids and inflammation as causing disease. Schwartz and colleagues instead asked whether it might be considered as a form of "remodeling," in which the cells reorganize the structure of the tissue. In the study, the Yale-led research team focused on the link between remodeling of the extracellular matrix—the fibrous tissue around the cells—and inflammation. They found that in mice, altering the signals from the receptors that bind extracellular matrix reduced inflammation and atherosclerosis. By revealing how matrix remodeling controls inflammation, the work identifies a possible new target for atherosclerosis.
The second study was a collaboration with the lab of Anne Eichmann, also in cardiology. The Eichmann lab studies a condition called hereditary hemorraghic telangiectasia (HHT) in which blood vessels are malformed, leading to bleeding in the skin, nose, and other organs. HHT is due to mutations in two cell receptors for proteins in the blood called BMPs. This research team found that how these receptors signal strongly depends on both the BMPs and the force from flowing blood. HHT patient blood vessels are poorly formed because they do not respond properly to blood flow. The results deepen our general understanding of how blood vessel structure is regulated, and point to potential therapeutic targets for HHT and other common vascular diseases, they said. Read the study published in the Journal of Cell Biology.

Explore further: Understanding adverse blood vessel remodeling following stenting

More information: Nicolas Baeyens et al. Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia, The Journal of Cell Biology (2016). DOI: 10.1083/jcb.201603106
Sanguk Yun et al. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling, Nature Cell Biology (2016). DOI: 10.1038/ncb3405

Journal reference: Nature Cell Biology Journal of Cell Biology
Provided by: Yale University

Gene helps prevent heart attack, stroke - and may offer way to block effects of aging

Don't worry, nothing will be done to follow this up for decades, not in time to help your children or grandchildren.
http://www.mdlinx.com/internal-medicine/medical-news-article/2016/05/26/6680593/?news_id=2386&newsdt=052816&subspec_id=1531&utm_source=WeeklyNL&utm_medium=newsletter&utm_content=Weeks-Best-Article&utm_campaign=article-section&category=latest-weekly

University of Virginia Health System News, 05/26/2016

A gene that scientific dogma insists is inactive in adults actually plays a vital role in preventing the underlying cause of most heart attacks and strokes, researchers at the School of Medicine have determined. The discovery opens a new avenue for battling those deadly conditions, and it raises the tantalizing prospect that doctors could use the gene to prevent or delay at least some of the effects of aging. “Finding a way to augment the expression of this gene in adult cells may have profound implications for promoting health and possibly reversing some of the detrimental effects with aging,” said researcher Gary K. Owens, PhD, director of UVA’s Robert M. Berne Cardiovascular Research Center. The researchers found that Oct4 controls the movement of smooth muscle cells into protective fibrous “caps” inside the plaques – caps that make the plaques less likely to rupture. The researchers also have provided evidence that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques. This is exciting, because studies suggest that it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a means to reduce the incidence of heart attacks or stroke. “Our findings have major implications regarding possible novel therapeutic approaches for promoting stabilization of atherosclerotic plaques,” said Olga A. Cherepanova, PhD, a senior research scientist in Owens’ lab. One surprising finding from UVA’s research: When the researchers blocked the effect of Oct4 in mice, they thought the atherosclerotic plaques might become smaller, because of the reduced number of smooth muscle cells inside. Instead, the plaques grew larger, less stable and more dangerous, stuffed with lipids, dead cells and other damaging components. The discovery was described in a paper published online by the journal Nature Medicine.