Abstract 1209: Bone Morphogenic Protein-4 is Elevated in Chronic Kidney Disease Patients with Coronary Artery Disease
Cross-sectional studies have demonstrated that the Framingham Risk Equation does not adequately predict the magnitude of the increased risk of cardiovascular disease seen in chronic kidney disease (CKD) patients, suggesting additional risk factors may be present in CKD patients. Recent studies suggest that the increased vascular calcification seen in CKD patients compared with the general population may play a role in the increased risk of cardiovascular events. One mechanism proposed for the induction of vascular calcification is the up-regulation of the bone morphogenic proteins (BMP) at the site of vascular calcification. We measured the levels of BMP-4 in the plasma of healthy volunteers (n=11) and patients with coronary artery disease (CAD) without CKD (n=10), CKD without CAD (n=6), and CKD with CAD (n=7). CKD was defined as Stage 3, 4, or 5 kidney disease using the National Kidney Foundation’s KDOQI classification. CAD was defined as a greater than 50% narrowing of a coronary artery determined angiographically. A statistically significant elevation of BMP-4 in the plasma of patients with both CAD and CKD was observed. In order to elucidate the possible role of BMP-4 in vascular calcification, we treated vascular smooth muscle cells (VSMCs) with10 μM of BMP-4 for 10 days and then stained for calcium deposition. Treatment of VSMCs with BMP-4 led to significant calcium deposition similar to a positive control (50 mM β-glycerophosphate) as well as a morphological change more closely resembling osteoblasts than VSMCs. These data suggest that CDK patients with elevated BMP-4 serum levels are at a greater risk for CAD due to increased vascular calcification.