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Journal of Lipid Research, Vol. 43, 1618-1629, October 2002
Copyright © 2002 by Lipid Research, Inc.

Increased atherosclerosis in diabetic dyslipidemic swine

Joseph L. Dixon^1,*,**, Siming Shen, James P. Vuchetich^**, Elzbieta Wysocka^*, Grace Y. Sun^,** and Michael Sturek^*,,**

^* Dalton Cardiovascular Research Center, University of Missouri, Research Park, Columbia, MO
Department of Biochemistry, University of Missouri, Research Park, Columbia, MO
Departments of Physiology and Internal Medicine, School of Medicine, University of Missouri, Research Park, Columbia, MO
^** Diabetes & Cardiovascular Biology Program, University of Missouri, Research Park, Columbia, MO

¹ To whom correspondence should be addressed. e-mail: dixonj{at}missouri.edu

Male Yucatan swine were allocated to four groups (n = 5–6 pigs per group): low fat (3%) fed control, high fat/2% cholesterol (CH) fed (HF), high fat/CH fed with alloxan-induced diabetes (DF) and DF pigs that were treated with atorvastatin (80 mg/day; DF+A). Pigs were fed two meals per day and daily insulin injections were used in diabetic pigs to maintain plasma glucose between 250 and 350 mg/dl. Diabetic dyslipidemic (DF) pigs exhibited greater coronary atherosclerosis and increased collagen deposition in internal mammary artery compared with normoglycemic hyperlipidemic pigs. Although total and LDL CH concentrations did not differ, triglyceride (TG) were increased in DF pigs and FPLC analysis indicated that the LDL/HDL CH ratio was significantly increased in DF compared with HF pigs. The LDL fraction of DF pigs contained larger, lipid enriched particles resembling IDL. Consumption of the high fat/CH diet caused a moderate increase in the percentage of 14:0 fatty acids in plasma lipids and this was compensated by small-moderate declines in several unsaturated fatty acids. There was a significant increase in phospholipid arachidonic acid in DF compared with HF pigs. Atorvastatin protected diabetic pigs from atherosclerosis and decreased total and VLDL TG, but exerted minimal effects on the FPLC lipoprotein and plasma fatty acid profiles and plasma concentrations of total and LDL CH, vitamin A, vitamin E, and lysophosphatidylcholine. Across all groups the plasma CH concentration was positively correlated with hepatic CH concentration.

These findings suggest that atorvastatin's protection against coronary artery atherosclerosis in diabetes may involve effects on plasma VLDL TG concentration. Lack of major effects on other lipid parameters, including the LDL/HDL ratio, suggests that atorvastatin may have yet other anti-atherogenic effects, possibly directly in the vessel wall.

Abbreviations: CAD, coronary artery disease; CE, cholesteryl esters; CFX, circumflex; CH, cholesterol; DF, high fat/CH fed pigs with alloxan-induced diabetes; DF+A, high fat/CH fed pigs with alloxan-induced diabetes treated with atorvastatin; GC, gas chromatograph; HF or F, high fat/2% cholesterol fed pigs; HPTLC, high performance thin layer chromatography; LAD, left anterior descending; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; PL, phospholipids; TG, triglyceride

Supplementary key words Yucatan miniature swine • LDL • HDL • remnants • cholesterol • triglycerides • hypertriglyceridemia • endothelium • vascular smooth muscle • coronary artery • statin • vitamin E • arachidonic acid

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