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In a new study at the University of Virginia School of Medicine, scientists led by Dr. Mete Sibelek have made a major advance in understanding cardiovascular disease. Specifically, we studied in detail atherosclerosis, which is hardening of the arteries due to the buildup of fatty plaques.

Atherosclerosis causes a fibrous cap to form over the plaque, which acts as a protective barrier to prevent it from sloughing off and causing a heart attack or stroke. Dr Sibelek’s team focused on the biological “scaffolding” built on top of plaque, seeing it as the key to combating the biggest cause of death worldwide.

Lifesaving treatment for cardiovascular disease

This innovative approach combined two decades of discoveries in human genetics with a unique collection of smooth muscle cells from arteries. This combination targeted the site of origin of these plaques.

“We discovered that our genetic makeup influences the way smooth muscle cells secrete proteins that give strength to plaques and prevent them from rupturing,” explains Dr. Sibelek, adding that these insights highlighted its potential to lead to life-saving treatment.

The role of cell adhesives in heart health

The study pays close attention to the “extracellular matrix,” a protein-rich glue-like substance secreted by smooth muscle cells. As a result, it forms a protective scaffold over the plaque, ensuring structural integrity and support.

The research team diligently followed the trail by carefully analyzing these proteins in the cells of 123 heart transplant donors. The goal was to highlight the genetic contribution and identify the genes involved in their fecundity.

important new insights

This exhaustive process revealed 20 gene locations directly associated with key proteins, revealing complex relationships. Furthermore, we precisely identified genetic variants that are significantly associated with increased risk. This variation has a particular impact on arterial stiffness and highlights potential targets for therapeutic intervention.

These findings are critical in identifying individuals at high risk for plaque rupture and provide new avenues for preventive care.

Furthermore, this study revealed the dual nature of smooth muscle cell efforts in plaque formation, sometimes protective and sometimes harmful. This nuanced understanding opens the door to targeted treatments for atherosclerosis and related cardiovascular diseases.

One particular protein, LTBP1, has emerged as playing an important role in plaque stability. “We have identified LTBP1 as a key factor in the stability of these plaques,” Civelek said, highlighting the team’s efforts to further study this protein as a therapeutic target.

Paving the way to personalized medicine

The University of Virginia research represents an important advance in the treatment of cardiovascular disease and significantly advances our understanding.

Importantly, by linking genetic factors to the body’s defenses against arterial plaques, this study provides a personalized medicine roadmap and strengthens our understanding of cardiovascular risk. This research could also pave the way for innovative treatments that could significantly reduce the global burden of heart disease.

As Dr. Sibelek and his team continue their research, a focus on translating research findings to patient care remains a top priority. With a better understanding of the genetic basis of atherosclerosis and cardiovascular disease, the medical community is now poised to develop tailored treatments, bringing hope to the world.

Learn more about cardiovascular disease

Cardiovascular disease (CVD) refers to diseases that affect the heart and blood vessels and is a major cause of morbidity and mortality worldwide. CVD encompasses a variety of conditions, each with its own causes, symptoms, and treatments.

coronary artery disease

One common form of CVD is coronary artery disease (CAD), which is characterized by the buildup of plaque within the coronary arteries that supply blood to the heart. This buildup can cause chest pain, heart attack, and other serious complications.

stroke

Another important category of CVD is stroke. A stroke occurs when blood flow to part of the brain is cut off, causing brain damage and various long-term disabilities.

Additional formats of CVD

Other forms of cardiovascular disease include heart failure, a condition in which the heart is unable to effectively pump blood throughout the body. Arrhythmia is an irregular heartbeat that affects how the heart works. Heart valve problems are when the valves that control blood flow in and out of the heart chambers don’t work properly.

Risk factor

Risk factors for developing CVD include high blood pressure, high cholesterol, smoking, diabetes, obesity, lack of exercise, and an unhealthy diet.

Prevention and treatment

Prevention and treatment strategies focus on managing these risk factors through lifestyle changes, medications, and sometimes surgical intervention.

Regular testing and monitoring are essential for early detection and management of the disease, ultimately improving outcomes and quality of life for those affected.

The research will be published in a journal Atherosclerosis, thrombosis, and vascular biology.

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