Endothelial Cell Dysfunction and Its Genetic Basis
Your blood vessels do more than carry blood. They are a living, dynamic system that keeps your heart and body running smoothly. One of the most important components of this system is the endothelial cells lining your blood vessels. When these cells malfunction, it can be an early warning sign of serious cardiovascular disease.
What Is Endothelial Cell Dysfunction?
Endothelial cells form a thin, protective lining inside all blood vessels. These cells help keep your cardiovascular system healthy by regulating blood flow, controlling inflammation, preventing abnormal clotting, and allowing blood vessels to widen or narrow as needed.
Endothelial cell dysfunction occurs when this lining no longer works properly. Instead of promoting smooth blood flow, dysfunctional endothelial cells lose their ability to relax blood vessels, regulate inflammation, and maintain vascular balance. This dysfunction often results in blood vessels becoming too stiff or narrowed, making it harder for blood to circulate efficiently.
A major problem in endothelial cell dysfunction is that the body produces less nitric oxide, a molecule that helps blood vessels relax and keeps blood pressure healthy. On top of that, higher levels of inflammation and oxidative stress can further harm these cells, speeding up damage to your blood vessels.
Endothelial cell dysfunction is considered one of the earliest detectable changes in the development of atherosclerosis, a condition where plaque builds up inside the arteries, narrowing them and making it harder for blood to flow. Even before plaque visibly forms in the arteries, impaired endothelial function can signal increased cardiovascular risk. Over time, this dysfunction contributes to plaque buildup, restricted blood flow, and the progression of coronary artery disease and peripheral artery disease.
Researchers are actively studying how genetic changes may influence endothelial cell dysfunction. While it is not yet fully understood which genes directly cause this condition, early research suggests that variations in certain genes may affect endothelial cell behavior, inflammation, and vascular repair, increasing susceptibility to cardiovascular disease.
Genetic Causes and Heart Risk Related to Familial Hypercholesterolemia and Cholesterol
Another area of research interest related to vascular issues is familial hypercholesterolemia. This genetically inherited condition alters how the body recycles low-density lipoprotein, also known as LDL or “bad” cholesterol.
Those born with the condition have high LDL cholesterol levels at birth. As most people age, their LDL levels tend to rise. People with familial hypercholesterolemia also see increased LDL levels as they age, but they have the disadvantage of starting at a higher level than other people.
High LDL levels are known to lead to plaque buildup, which can raise the risk of coronary heart disease. If left untreated, people with familial hypercholesterolemia are 20 times more likely to develop heart disease.
Genes Linked to Familial Hypercholesterolemia
Researchers have identified three genes as being related to familial hypercholesterolemia. One is a mutation in the gene for the LDL cholesterol receptor. The PCSK9 gene and the gene for Apolipoprotein B can also cause you to inherit familial hypercholesterolemia.
As scientists learn more about the genes responsible for the condition, there are lifestyle and drug treatments available to help counteract familial hypercholesterolemia. In most cases diet and exercise help, but medications are usually needed to treat those with familial hypercholesterolemia.
Treatment usually calls for statin drugs, though a class of lipid-lowering medications called bile acid sequestrants, may also be used. Bile acid sequestrants lower the amount of cholesterol absorbed by the intestines, which then lowers the amount of cholesterol entering the bloodstream.
If you live with familial hypercholesterolemia, consult with your healthcare provider to determine the best course of action to bring your cholesterol levels down.
Hutchinson-Gilford Progeria Syndrome and Cardiovascular Genetics
Hutchinson-Gilford Progeria Syndrome, referred to as HGPS or progeria, is a rare genetic condition that leads to devastating cardiovascular outcomes. About 1 in 18 million people develop this genetic mutation. Children who are diagnosed with this disorder, with treatment, can live into their early 20s.
Mutations in the LMNA gene are thought to be the main culprit in this disorder. It can lead to early cardiovascular disease including heart attack, stroke, or heart failure.
Scientists trying to solve this premature aging disorder are looking at the use of induced pluripotent stem cells from HGPS patients to study the condition more efficiently. Finding better ways to mimic the condition in the lab could lead to new treatment options that can hopefully help these children live longer lives. Induced pluripotent stem cells are made from skin or blood cells that are reprogrammed to become stem cells that can produce a wide range of cell types.
This type of research could also improve health for adults who develop cardiovascular conditions later in life. Even in people who do not have HGPS, they will experience progerin accumulating in vascular cells as they age.
Nitric Oxide, Endothelial Cells, and Heart Health
Another component in keeping your vascular system operating efficiently is nitric oxide. This molecule helps in an array of cell functions, including some related to endothelial cells in the vascular system. Nitric oxide synthases, or NOS, are enzymes that produce nitric oxide in the body.
Researchers are interested in a variant known as endothelial NOS3 which can alter the production of nitric oxide. This could lead to new research targets to improve future blood pressure control treatment options.
Endothelial Cell Dysfunction Treatment Options
People with endothelial dysfunction often have blood vessels that cannot widen properly, which can limit blood flow and make the vessels functionally narrower than normal. Any disruption in proper blood flow can lead to problems with heart health.
Over time, this may contribute to coronary or peripheral artery disease, making treatment important. Potential treatment options for this type of patient include:
- Aspirin
- Blood pressure medications
- Cholesterol-lowering drugs
- Nitrates
Dietary and lifestyle changes can also help those who have endothelial dysfunction. Options range from adopting a heart-healthy diet and exercising to limiting alcohol consumption and lowering stress levels.
As with any major change in lifestyle or the start of a medication, consult with your healthcare professional to discuss the risks and benefits of each option.
How Genetics Can Inform Your Heart Health Decisions
If you live with any of the conditions discussed, be sure to consult with your healthcare provider for treatment options or lifestyle recommendations. Having an understanding of your genetic risk can help you and your provider make more informed decisions to protect your heart and vascular health.
Visit the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) website to keep up with the latest in heart research and treatment options.
