Single gene may trigger arterial hardening

YALE (US)—Researchers have identified a single gene that plays a key role in the development of atherosclerosis in mice, a discovery that could shed light on the causes of coronary artery disease and related conditions.

Atherosclerosis, or the hardening of the arteries, is caused by a buildup of plaque in the arterial wall. Until now, scientists have not understood how the plaque, known as low-density lipoprotein (LDL) cholesterol, infiltrates the vascular lining. The Yale University team discovered that, when active, the caveolin-1 (Cav-1) gene—which is essential for orchestrating certain intracellular trafficking—promoted atherosclerotic lesions.

The researchers fed mice a high-cholesterol diet for 12 weeks and found that atherosclerotic plaques were clearly visible in mice that expressed the Cav-1 gene in their endothelial linings. But they also found that in mice where the Cav-1 gene was absent, the number and size of aortic plaques were dramatically lower.

According to lead author William C. Sessa of the Yale School of Medicine, the study offers physiological evidence of the gene’s role and “indicates that Cav-1 may regulate the entry of LDL into the vessel wall, which begins the process of atherosclerosis.”

How might this revealing research on mice be applied to atherosclerosis in humans?

“Most drugs used to treat atherosclerosis do so by reducing LDL cholesterol levels. Although this approach is highly successful, it has been a mystery for decades as to how LDL gets from the blood into the vessel wall to initiate atherosclerosis,” says Sessa. “Our work strongly implicates caveolin-1 and suggests that despite the presence of elevated lipids, inhibitors of this pathway may reduce atherosclerosis and coronary artery disease”.

Researchers from Yale and the Universidad de Alcala in Madrid contributed to the study. This research was funded by grants from the National Institutes of Health, American Heart Association, and Ministerio de Educacion y Ciencia, Spain. Findings appear in the July 8 issue of the journal Cell Metabolism.

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