Patient’s vital signs on ICU monitor, isolated closeup, dutched left
Scientists at the School of Medicine have identified a potential way to head off heart attacks and strokes by strengthening the fibrous caps overlying atherosclerotic plaques that naturally accumulate inside our arteries. These fatty lesions can rupture, triggering blood clots that cause disability or death.
New research from the lab of UVA’s Gary K. Owens, PhD, reveals surprising new information about the makeup of the protective caps our bodies build over these lesions, and about the factors that determine their stability. This study supports recent findings that certain types of inflammation might actually help stabilize plaques. Doctors may one day be able to use these insights to strengthen the caps and prevent the plaques from rupturing.
“These studies redefine our understanding of both how the caps form and what makes them strong,” said Owens, the head of UVA’s Robert M. Berne Cardiovascular Research Center and a member of UVA’s Departments of Molecular Physiology and Biological Physics and Internal Medicine (Division of Cardiology). “These studies were completed by a large team of highly talented investigators from UVA and abroad but led by three outstanding trainees from my laboratory, including co-first authors Alexandra Newman [PhD], Vlad Serbulea [PhD] and Richard Baylis [MD/PhD].”
Unstable atherosclerotic plaques account for the majority of heart attacks and a large fraction of strokes, making these lesions the leading cause of death worldwide. The protective caps our bodies create over these lesions act like a patch on a tire, preventing them from rupturing and triggering catastrophic blood clot formation, which, in blood vessels supplying the heart or brain, can cause a heart attack or stroke. Therefore, improving our understanding of how the cap forms is of major clinical importance. “Despite decades of research, little is known regarding the factors and mechanisms that promote formation and maintenance of a stable fibrous cap,” the UVA researchers write in a new scientific paper outlining their findings.
This work from Owens and his team helps change that, offering unexpected insights into the caps’ composition and origins. Scientists have thought that the caps were derived almost exclusively from smooth muscle cells, but Owens’ findings reveal that there is a “tapestry” of different cell types involved. “For years we assumed that most of the protective fibrous cap cells were of smooth muscle cell origin because that’s what they look like under the microscope,” Newman said, adding, “Advanced techniques show us how dynamic this structure really is.”
Baylis noted that “having multiple cell types contribute to the fibrous cap likely make this critically important structure more robust and resistant to plaque rupture.”
Up to 40% of the fibrous cells in the cap in lab mice come from sources other than smooth muscle cells, the researchers found. In advanced human lesions, approximately 20%-25% of the fibrous cap cells came from other sources. Those other sources include endothelial cells – cells that line our blood vessels – and immune cells called macrophages, typically viewed as being pro-inflammatory and plaque de-stabilizing, that have undergone special transitions that enable them to perform plaque-stabilizing functions.
The researchers went on to provide evidence that the formation of the fibrous cap is dependent on metabolic re-programming of these cells to perform processes that are essential to plaque stabilization. The findings suggest that clinicians may one day be able to treat the underlying causes of heart attacks and strokes by enhancing these transitions through novel drug therapies and dietary modifications to help ensure patients have stable caps.
“Our studies unveil a potential new approach for reducing the probability of plaque rupture, which could be used in conjunction with current therapies that focus on lowering cholesterol and preventing clot formation,” Owens said.
“This paradigm-shifting study presents evidence for beneficial roles of other cell types and mechanisms driving plaque stabilization,” Serbulea explained. He added that in conjunction with previous studies from the lab, these findings provide evidence that “inflammation, often the scapegoat for heart disease, seems to reprogram endothelial cells and macrophages to help stabilize plaques.”
Taking the new results in consideration with recent clinical trials such as CANTOS, TINSAL-CVD and CIRT that have shown little to no benefit of global anti-inflammatory therapies, the UVA team is urging researchers and pharmaceutical companies to rethink their approaches to preventing heart attacks and strokes.
Original Article: Discovery Reveals Potential Way to Prevent Heart Attacks, Strokes
More from: University of Virginia
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- Atherosclerosis no. 1 cause of death in Richmond area, heart attacks no. 3
Frances Givens, of Bon Air, began to feel dizzy while coming out of a department store. She didn’t pass or fall down. There were no headaches or chest ...
- Navidea Biopharmaceuticals Announces Publication of Study Examining Tc99m Tilmanocept Imaging of Arterial Inflammation in People with HIV
Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) (“Navidea” or the “Company”), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, today announced ...
- This One Factor Can Predict a Heart Attack, Says MD
Heart attacks seem like they happen out of nowhere, but oftentimes there are warning signs that were missed. Nobody thinks they're going to have a heart attack, but every 40 seconds someone in the ...
- Established drug for symptoms of angina pectoris also protects vascular system, study finds
A drug used in the clinical treatment of angina symptoms also has an anti-inflammatory effect and reduces atherosclerotic plaques in blood vessels -- thereby reducing the risk of heart attack or ...
- Long-established drug for angina pectoris shows anti-inflammatory effect, reduces atherosclerotic plaques
It has an anti-inflammatory effect and reduces atherosclerotic plaques in our mouse models. These plaques also become more stable, potentially significantly reducing the risk of heart attack." ...
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Soligenix Receives Agreement from FDA on Initial Pediatric Study Plan for HyBryte(TM) for the Treatment of Cutaneous T-Cell Lymphoma
Additional analyses also indicated that HyBryte™ is equally effective in treating both plaque (response 42% ... our vaccine programs incorporates the use of our proprietary heat stabilization platform ...
- Soligenix Receives Agreement from FDA on Initial Pediatric Study Plan for HyBryte™ for the Treatment of Cutaneous T-Cell Lymphoma
Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet ...
- HyBryte™ Phase 3 FLASH Study for the Treatment of Cutaneous T-Cell Lymphoma Published in JAMA Dermatology
The published findings demonstrate that HyBryte™ treatment statistically significantly reduced lesion size, with the treatment response further improving over successive 6-week ...