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Damage to dead cell disposal system may increase heart disease

Damage to dead cell disposal system may increase heart disease

garbage cansThink of it like taking out the garbage.

That’s the way Stanford researcher Nicholas Leeper, MD, explained to me the findings of his recently published study.

Actually, it’s more helpful to think of the study’s discoveries on the genetics of heart disease as something of a garbage strike – at the molecular level.

Due to a genetic defect, the body’s ability to dispose of its daily tonnage of dead cells gets damaged, and as a result the body’s garbage - in the form of old cells and debris - starts to build up in the walls of its blood vessels. Normally, the body is extremely efficient at taking out the garbage. Two hundred billion cells die every day in our bodies and most get cleared out within a matter of seconds. But when this process breaks down and garbage in the form of necrotic cells starts building up in the walls of blood vessels, it’s not a good thing.

Leeper, a physician and assistant professor of vascular surgery, and colleagues Yoko Kojima, MD, Tom Quertermous, MD, and others set out to discover why genetic variation at the chromosome 9p21 location has been repeatedly identified as the most important commonly inherited DNA sequence for a wide range of cardiovascular diseases including stroke, heart attacks and aneurysms.

Conducting studies in mice with atherosclerosis, the researchers showed that loss of a candidate gene at this locus leads to impaired “efferocytosis” - from the Latin for “take to the grave” – the process by which dead or necrotic cells are removed. Literally, the burying of dead cells. Mice with this genetic variation showed an increase in buildup of these dead cells, further advancing their atherosclerosis as opposed to those that did not have the genetic variation.

In other words, a commonly inherited genetic variant, which is found in 20 percent of the population, contributes to the development of coronary artery disease (also known as coronary atherosclerosis) by stimulating the accumulation of necrotic debris within the evolving plaque. Coronary atherosclerosis is the process by which plaque builds up in the wall of heart vessels, eventually leading to chest pain and potentially lethal heart attacks. Leeper explained it to me further:

If you were born with genetic variation at the 9p21 locus, your risk of heart disease is elevated, though we haven’t understood why. This research gets at that hidden risk. You can be a non-smoker, be thin, have low blood pressure, and still be at risk for a heart attack if you were born with this variant. This work may help explain that inherited risk factor, and more importantly help develop a new therapy to prevent the heritable component of cardiovascular disease.

Photo by shooting brooklyn

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