Influence Of Atherosclerosis And Exercise On Arterial Lipoprotein Lipase Activity In Pigs

Abstract

INTRODUCTION: Lipoprotein lipase (LPL) has repeatedly been identified as one of the major susceptibility genes for human coronary artery disease. The LPL protein is detectable both in peripheral tissues such as adipose tissue and skeletal muscle and also in conduit arteries such as the thoracic aorta. However, the functional enzyme activity has heretofore never been quantified in arteries with respect to either vascular disease or exercise training. We have overcome prior experimental limitations by utilizing a porcine model of atherosclerosis, where the endothelium from large arterial samples could be obtained in conjunction with modifications in the LPL assay to improve accuracy. PURPOSE: The primary purpose was to determine the effects of exercise training on arterial LPL activity in a porcine model of atherosclerosis. METHODS: Heparin releasable LPL (HR-LPL) activity was measured in approximately 5.2 cm2 of the thoracic aorta, and also in skeletal muscle and adipose tissue. In keeping with the purpose, a pig strain with familial hypercholesterolemia (FH) was run trained for ∼5 months and compared to controls fed an identical diet (N=13 run trained and N=12 untrained). As a basis of comparison to generally healthy pigs, LPL was measured in another strain of pigs with substantially lower plasma cholesterol (Yucatan). RESULTS: There was about twice as much arterial HR-LPL activity in FH pigs after the exercise training compared to sedentary control FH pigs (40±4 vs. 19±3 mU/mg total protein; p<0.05). This two-fold training effect for artery HR-LPL was evident in both males and females. In contrast to this, neither skeletal muscle, nor adipose HR-LPL activity was altered by the exercise training. Blood lipoproteins were not improved by exercise. Paradoxically, arterial HR-LPL activity was 13.7 fold greater in FH pigs (21.3±4.6 mU/mg) compared to the Yucatan pigs (1.6±0.2 mU/mg). CONCLUSION: Exercise run training increased arterial HR-LPL activity in a porcine model of lipoprotein-induced atherosclerosis. Supported by NIH HL02490