Yale Researchers Identify Gene's Role In Promoting Atherosclerosis

Main Category: Cardiovascular / Cardiology
Also Included In: Vascular
Article Date: 09 Jul 2009 - 1:00 PDT

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Yale University researchers have found that a single gene plays a key role in the development of atherosclerosis in mice. The research provides insight into the causes of atherosclerosis, or the hardening of the arteries caused by a buildup of plaque.

The research appears in the July 8th issue of the journal Cell Metabolism.

Accumulation of low-density lipoprotein (LDL) cholesterol in the artery wall is the initial event in atherosclerosis, but the mechanism of how the LDL infiltrates vascular lining to reach the arterial wall has been unclear. The Yale 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, Ph.D., of the Yale School of Medicine, "This study of mice provides physiological evidence of the important role of Cav-1 expression in the endothelial lining of blood vessels 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? Dr. Sessa says, "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. 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".

Other researchers include: Carlos Fernandez-Hernando, Jun Yu, Yajaira Suarez, Christoph Rahner and Alberto Davalos of the Vascular Biology & Therapeutics Program in the Yale School of Medicine, and Miguel A. Lasuncion of Universidad de Alcala, Madrid.

This research was funded by grants from the National Institutes of Health, American Heart Association and Ministerio de Educacion y Ciencia, Spain.

Source
Yale University

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