@article {Liu:November 1997:0920-3206:659,
	author = "Liu, Rui",
	author = "Saku, Keijiro",
	author = "Jimi, Shiro",
	author = "Ohta, Takao",
	author = "Zhang, Bo",
	author = "Takebayashi, Shigeo",
	author = "Arakawa, Kikuo",
	title = "Mechanism of Action of Gemfibrozil on HDL Metabolism and Atherosclerosis in WHHL Rabbits",
	journal = "Cardiovascular Drugs and Therapy",
	volume = "11",
	year = "November 1997",
	abstract = "We investigated the mechanism of action of gemfibrozil on high-density lipoproteins (HDL) and apolipoprotein (apo) A-I metabolism and atherogenesis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia and HDL deficiency. Two-month-old WHHL rabbits were fed either a normal control diet or a diet containing 0.5% gemfibrozil for 12 months. In vivo apo A-I kinetics, the fractional rate of cholesterol esterification in HDL (FER<SUB>HDL</SUB>), which reflects the reactivity of HDL to lecithin:cholesterol acyltransferase, and a morphometrical analysis of atherosclerotic lesions in the descending thoracic aorta, were examined. At12 months, the mean levels of serum total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in both groups had decreased to approximately 53%, 57%, and 87% of the initial levels (at 0 month), respectively, which is characteristic of homozygous WHHL rabbits of the physiologic influence of aging, and no differences in the levels of serum LDL-C, HDL-C, and triglycerides were found between the two groups. Rabbits treated with gemfibrozil exhibited a decreased FER<SUB>HDL</SUB> (38% of the controls, P = 0.039). Gemfibrozil induced a significant increase in the total mass of apo A-I (1.7-fold, P &#60; 0.05) and in the rate of apo A-I synthesis (1.6-fold, P&#60; 0.05). The atherosclerotic intimal area was positively correlated with serum LDL-C (P = 0.02) in both groups, but gemfibrozil did not affect the atherosclerotic intimal area. These results indicate that 12 months of treatment with gemfibrozil did not protect against atherosclerosis despite a significant increase in apo A-I synthesis and enhanced HDL function through FER<SUB>HDL</SUB>. It is possible that both the qualitative and quantitative improvement in HDL by gemfibrozil cannot overcome the massive and long-term exposure of the vascular wall to LDL in these animals.",
	pages = "659-668(10)",
	url = "http://www.ingentaconnect.com/content/klu/card/1997/00000011/00000005/00147627"
	doi = "doi:10.1023/A:1007786908171"
}