Abstract 641: Hypotrophic Vascular Remodeling Associates With Vascular Calcification in vivo in Vitamin D3-stimulated Leptin-deficient ob/ob Mice

Vascular calcification may determine arterial flow imbalance through increasing vascular rigidity and Windkessel effect, frequently occurring in diabetes. Vascular remodeling, considered an adaptive response of the vessel to specific stimuli, may associate with calcification and participate in pathophysiology of cardiovascular disease. In order to further investigate the intersection between pathophysiology of vascular calcification and vascular remodeling, we hypothesized that leptin-deficient ob/ob mice, demonstrate increased vascular remodeling and vascular calcifying response to Vitamin D3 in vivo compared to C57BL/6 (C57) mice. We injected C57 and ob/ob mice with Vitamin D3 8x104IU (VitD) daily or saline 0.9% ip. (Cont) for 14 days and for 21 days. Results are showed as Mean±SEM. We considered statistically significant if p<.05 after ANOVA (Newman-Keuls). After 14d, o b/ob VitD aorta decreased aortic wall thickness (24.3±0.4μm) versus ob/ob Cont (29.7±1.3μm), vs. C57VitD (34.4±0.6μm) and vs. C57Cont (39±1.3μm), p<.05 n=6. After 21d, we also showed that ob/ob VitD decreased aortic wall thickness (25.4±0.5μm) vs. ob/ob Cont (29.7±1.3μm) and vs. C57Cont (39.0±1.3μm), p<.05 n=3. Moreover, o b/ob VitD decreased vessel wall area (VWA)= 79120±3957μm2 vs. ob/ob Cont=85310±4593μm2 and vs. C57Cont=96970±6719μm2 after 14d (n=6) and also after 21d ( ob/ob VitD=72090±3268μm2 vs. ob/ob Cont=85310±4593μm2(n=3). On contrary, C57VitD did not change VWA. Coincidently, ob/ob VitD increased vascular calcification after 14d (total Ca++ area burden=4548.2μm2, n=6) and after 21d (total Ca++ area burden=2212.88 μm2, n=3) respectively. C57VitD and C57Cont did not calcify (n=6). Together with increased VWA loss and calcification, ob/ob VitD also showed augmented elastolysis and fibrosis. Nevertheless, hypotrophic remodeling did not determine any change in vascular lumen area ( ob/ob VitD=208300±24810μm2; ob/ob Cont=207300±22740μm2, C57VitD=196800±22120μm2 and C57Cont=225400±17960μm2) after 14d in this model. Vascular remodeling associated with calcification and other architectural changes of the vascular wall may bring important insights for investigating human cardiovascular disease in obese and insulin resistant background.