Abstract

It is known that high-cholesterol diet impairs coronary vasodilatation in animal models of athe-rosclerosis irrespective of overt pathology. We evaluated the specific role of LDL and HDL on adenosine-elicited coronary vasodilatation after short time (10 weeks) high-cholesterol diet in pigs. Nineteen pigs on standard (C), atherogenic (HF) and alternate standard or atherogenic diet every other week (IHF) underwent left coronary angiography and flow (CFR) measurement during intracoronary adenosine injection. Total cholesterol, HDL, LDL, Apo lipoprotein A-1, IL-6, TNF-α and ICAM-1 were measured and histology of coronary samples was performed. IHF and HF show comparable intimal thickening of lesions, similar cholesterol (598.4 ± 198.2 and 633.2 ± 83.5 mg/dL) and LDL (502.6 ± 193.7 and 576.1 ± 83.2), while HDL is double in IHF group (88.3 ± 6.4 vs 46.4 ± 18.7 p < 0.0001). Vasodilation is reduced in HF (CFR = 1.6 ± 0.2, p < 0.001) as compared to C (2.6 ± 0.4), whilst it is preserved in IHF (2.7 ± 0.4). CFR and HDL values of all hypercholesterolemia cases are positively correlated (r = 0.88, p < 0.001). No relation with cytokines/cell adhesion markers is present. These findings suggest for the first time that elevation of plasma HDL level counteracts LDL related vasodilation impairment during coronary atherogenesis in swine.

Highlights

  • The effect of hypercholesterolemia on coronary microvascularHow to cite this paper: Vozzi, F., et al (2014) High Density Lipoprotein (HDL)-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

  • A different contribution of total, Low density lipoprotein (LDL) and HDL cholesterol to the impairment of coronary reserve was evidenced from previous experimental studies, they demonstrated an inhibitory effect of oxidized LDL and a protective role of HDL only on endothelium-dependent arterial vasodilation [20], concordant with clinical observations [21] [22]

  • HDL, Total Cholesterol/HDL and LDL/HDL ratio were significantly higher in IHF and HF as compared to C group

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Summary

Introduction

The effect of hypercholesterolemia (total cholesterol and its lipoprotein fractions) on coronary microvascularHow to cite this paper: Vozzi, F., et al (2014) HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine. A different contribution of total, LDL and HDL cholesterol to the impairment of coronary reserve was evidenced from previous experimental studies, they demonstrated an inhibitory effect of oxidized LDL and a protective role of HDL only on endothelium-dependent arterial vasodilation [20], concordant with clinical observations [21] [22]. The amount and type of fat intake, even independently of cholesterol addition, is known to induce different anatomical and functional alterations at micro and macrovascular coronary level and a number of diet related factors have been shown to alter the amount of cholesterol carried in plasma LDL and HDL fractions and to drive their distinctive effects on coronary arteriolar vasodilator function [26]-[29]

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