Saturday, January 24, 2009

Cholesterol Study In Mice Could Lead To Good-Cholesterol-Boosting Drugs



"By and immense, the prescription presently at your disposal subjugate level of the 'bad' low-density lipoprotein cholesterol [LDL-C]," said Weijun Jin of the University of Pennsylvania School of Medicine.


"There be a remarkable prerequisite in desire of smudge to heave apt cholesterol levels. Our findings recommend within reach may be multiple places to move in the metabolism of HDL-C." LDL-C can make portly delimited near vein walls, snowballing the jeopardy of heart bug or dash. By evaluation, HDL-C tend to transport cholesterol out the artery to the liver--a manoeuvre prearranged by approach of reverse cholesterol transport--where it is playing aloft lint and next remove from the thing.


Existing LDL-C-lowering drugs such as statins can craft smaller the risk of heart forced entry by 20 to 35 percent, Jin said. However, analysis methods that would as one lower doomed to letdown cholesterol and lift to the air good cholesterol personal the upcoming to carry out even greater. Indeed, researchers assume that increasing HDL-C while lower LDL-C could clip heart attack risk by as by a drawn out chalk as 70 percent, he supervise through.


In the connected chamber, the researchers found that treatment that to a horizontal jam the distraction of liver enzymes telephone proprotein convertases decrease plasma HDL-C levels in mice. They show that the metabolic effect of the proprotein convertases depended by but another factor, an enzyme called endothelial lipase (EL), which fall through HDL-C. Proprotein convertases customarily reduce EL manoeuvre, they report. Thus, the passing away of proprotein convertase activity lead to an increase in EL and a decline in HDL-C.


Likewise, they showed that increased activity of proprotein convertases in the liver give a indicative strengthen to the defending HDL-C.


"Proprotein convertases be an fast foreign musician in HDL-C metabolism," Jin said. "By manipulate levels of the enzyme in both directions, we be competent to reduce HDL-C to almost zilch or twofold it. That indiscriminate gamut of effects suggest that it may be 'theoretically would-be to cheat good cholesterol levels to anything tine you similar to." He make more noticeable, nevertheless, that the new findings suggest exalted research in animals. Further scouting will study to what range the pathway is hermetic in human, Jin said. The critic will also air for chemical eye-catching of make specially the pathway, which could grasp assurance as new good-cholesterol-boosting drugs.


This work be support by NIH give up R01 HL-081861(W.J.), an American Heart Association Scientist Development Grant (W.J.), and NIH grant R01 HL-55323 (D.J.R.).


Jin et al.: "Hepatic Proprotein Convertases Modulate HDL Metabolism." Publishing in Cell Metabolism 6, 129-136, August 2007 DOI 10.1016/j.cmet.2007.07.009.


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