Coronary artery placenta growth factor expression is reduced by diabetes and hyperlipidemia

Abstract

Diabetics have both a higher risk of coronary artery disease (CAD) and a poorer prognosis from CAD than non-diabetics, which might be explained in part by blunted coronary collateral artery enlargement (arteriogenesis). Placenta growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, is arteriogenic. Thus, we hypothesized that PlGF levels would be reduced in diabetes. We assessed PlGF gene expression in left anterior descending (LAD) coronary artery using real-time quantitative RT-PCR. In swine made diabetic with alloxan and fed a moderately high-fat/cholesterol diet (46% kcal from fat, 2% cholesterol) (DD, N=2), PlGF mRNA was reduced to ~20% of control (C, N=10) (p=0.04). To assess the effect of the high-fat diet separately from hyperglycemia, we measured PlGF mRNA in swine fed either the moderately high-fat diet (H, N=11) or a very high-fat diet (75% kcal from fat) (H75, N=2). PlGF mRNA was significantly lower in H (~50% of C; p=0.02) and was further reduced in H75 (~15% of C; p=0.04). PlGF mRNA levels in swine fed a moderately high-fat diet and aerobically exercise trained (HX) were not different from C. Both Yucatan and Ossabaw swine showed a similar decrease in PlGF expression in response to the moderately high-fat diet. Thus, low PlGF levels may be a general feature of diabetes and the metabolic syndrome. Support: HL62552, RR13223, ADA (MS).