Abstract 14692: Low Dose Atorvastatin Improves Angiogenesis in a Porcine Model of Metabolic Syndrome
Objective: We developed a clinically relevant hypercholesterolemic swine model to evaluate the effect of atorvastatin on angiogenesis in the heart.
Methods: Sixteen Ossabaw pigs were fed a hypercholesterolemic diet or a hypercholesterolemic diet with atorvastatin (1.5mg/kg daily) for 14 weeks. All animals underwent placement of an ameroid constrictor to the circumflex artery to induce chronic ischemia and continued on their respective diets for 10 more weeks. All animals then underwent sternotomy, functional cardiac measurements and the non-ischemic normally perfused left ventricle was harvested for analysis of capillary and arteriolar density, myocardial perfusion, microvessel relaxation, and protein expression.
Results: Myocardial perfusion was similar in the OHC and OHCS groups with demand pacing (0.65±0.08 vs. 0.47±0.12ml/min/g p=0.25) and at rest (0.59±0.08 vs. 0.53±0.05ml/min/g p=0.53). Atorvastatin did not affect arteriolar density but increased capillary density and increased expression of pro-angiogenic protiens AKT, pAKT, VEGFR2, VEGF, and ENOS (see table and figure). The OHCS group had improved endothelium-dependent microvessel relaxation to adenosine diphosphate and endothelium-independent relaxation to sodium nitroprusside (see figure).
Conclusions: Atorvastatin treatment in a swine model of metabolic syndrome is associated with increased expression of pro-angiogenesis proteins and increased capillary density. Atorvastatin also improved microvessel relaxation. These results suggest that atorvastatin augments angiogenesis and reverses hypercholesterolemia induced endothelial dysfunction in swine with metabolic syndrome.
- © 2012 by American Heart Association, Inc.