Adenosine A1 Receptors in the Metabolic Syndrome and Coronary Artery Disease

Abstract

Atherosclerotic cardiovascular disease (CVD) involves narrowing or blockage of arteries. Metabolic syndrome, in humans, increases CVD risk. Previous studies from our lab have shown that activation of the adenosine A1 receptor (A1R) induces coronary smooth muscle cell proliferation; however, the association of A1R to CVD is unknown. The purposes of this study were to: compare the effects of a high fat (HF) diet on development of metabolic syndrome and CVD in swine models, determine whether A1R expression is altered by a HF diet and determine if macrophage infiltration is increased by a HF diet. Male Yucatan (Y) and Ossabaw (O) swine were treated for approximately 45 weeks with a normal low fat control diet (C) or a HF/2% cholesterol diet. Glucose and total cholesterol (TC) levels were obtained during glucose tolerance tests. Neointima formation was quantified using Verhoff-Van Gieson stain and macrophage infiltration was assessed by scavenger receptor B staining of the left main coronary artery. A1R receptor mRNA levels were measured in the left anterior descending coronary artery using real-time RT-PCR. HF to C glucose and neointima thickening ratios were greater in the O compared to the Y swine, ie.1.12 and 2.58 fold, respectively. TC increased 5–7 fold in O and Y swine, however, no significant difference in A1R mRNA expression was found between C and HF swine. Results suggest: O is a better model than Y swine for metabolic syndrome and CVD, the role of A1R is not clear and macrophage infiltration in HF O swine was 2 fold greater than C. Supported in part by Am. Diab. Assoc., NIH RR013223, HL062552, R25 GM067592 and P01 AI56097-02S1.