Renal Failure Linked to Cardiovascular Disease

One form of the enzyme cholesterol acyltransferase (ACAT), ACAT-2, has been found to be present in high levels in cases of chronic renal failure (CRF) and to contribute to the profound abnormalities of lipid metabolism and accelerated arteriosclerotic cardiovascular disease that characterize this condition. These findings were reported in the June 4, 2002, online version of the American Journal of Physiology: Endocrinology and Metabolism.

Investigators from the University of California, Irvine (USA; www.uci.edu) discovered that high levels of ACAT-2 in kidney failure accelerated the transport and storage of cholesterol into cells in the liver, which induced the liver to increase production of atherogenic very low density lipoproteins (VLDL) and other lipids as the liver sensed an apparent but false low level of cholesterol.

A rat model was developed to mimic chronic renal failure with high levels of ACAT-2. In these rats ACAT accelerated the production of VLDL. In rats that had normally functioning kidneys, ACAT-2 levels were normal, as were their cholesterol and lipid levels. While this study focused on the case of CRF, it is possible that this activation of ACAT-2 may also take place in the development of cardiovascular diseases that are not due to kidney failure.

While ACAT-2 is found in the liver, its close relative, ACAT-1, is an enzyme found in most other organs and tissues in the body. The research team, headed by Dr. D. N. Vaziri of the division of nephrology and hypertension at UC Irvine, is looking at whether inhibitors of ACAT-1 and ACAT-2 could help reduce the buildup of atherosclerotic plaque in the body.
"While our experiments were looking at kidney failure, we think that controlling ACAT production may be useful in combating atherosclerosis, regardless of its cause,” Dr.Vaziri said.



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