by Scientists at the University of Virginia School of Medicine have made significant discoveries related to strokes, heart attacks, and cardiovascular diseases by delving into the intricate biological mechanisms that safeguard our bodies from these life-threatening events. Led by Dr. Mete Civelek, the researchers focused on unraveling the factors influencing susceptibility to cardiovascular conditions like atherosclerosis, which is characterized by the accumulation of fatty plaques in the blood vessels. To shield against the risks of heart attacks and strokes posed by these plaques, the body forms fibrous caps over them.
In a bid to enhance the understanding of cardiovascular diseases—known to be the leading cause of global mortality—the team investigated the structural components surrounding these plaques, believing that they might offer crucial insights. By ingeniously integrating two decades worth of human genetics research with a specialized pool of smooth muscle cells, which are pivotal in the development of arterial plaques, the scientists made groundbreaking discoveries with the potential to revolutionize the development of life-saving therapies.
Dr. Civelek, from UVA’s Center for Public Health Genomics and the Department of Biomedical Engineering, explained, “We merged extensive human genetics data with a unique set of smooth muscle cells that play a key role in shaping the protective environment around plaques.” Through their research, the team uncovered that genetic variations influence the secretion of proteins by smooth muscle cells, fortifying the plaques and preventing catastrophic ruptures that trigger heart attacks and strokes. These proteins, forming an extracellular matrix akin to a glue-like structure rich in fibrous materials, are vital in reinforcing the protective shield over the plaques.
Analyzing smooth muscle cells sourced from 123 heart transplant donors, the researchers traced back the genes responsible for producing these critical proteins, identifying 20 genomic loci harboring genes that regulate their secretion. Moreover, they pinpointed a specific genetic variant that heightens the risk of arterial hardening in certain individuals and determined the specific protein types that contribute to cardiovascular vulnerabilities. This newfound knowledge could enable healthcare professionals to pinpoint high-risk patients prone to plaque rupture, fostering proactive interventions to avert heart attacks and strokes.
Furthermore, the study shed light on the dual nature of smooth muscle cell activities, elucidating why their actions can be both beneficial and detrimental in the context of cardiovascular health. Armed with this valuable insight, researchers anticipate the development of innovative treatments for atherosclerosis and related conditions.
Dr. Civelek highlighted, “We’ve identified a key protein, LTBP1, that potentially influences plaque stability, paving the way for exploring its therapeutic significance.” Building on this discovery, the team aims to investigate the therapeutic potential of this protein and translate their findings into tangible advancements in patient care in the near future.
