Abstract 350: Brown Adipose Tissue, a Novel Mechanism to Induce both Angiogenesis and Arteriogenesis

Abstract

Brown adipose tissue (BAT) is known to protect metabolism, but the extent to which it mediates angiogenesis and cardioprotection, the goal of this investigation, is not known. The Regulator of G Protein Signaling 14 (RGS14) knockout (KO) mouse is unique in that it not only extends longevity, but also enhances several aspects of healthful aging, i.e., protects against diabetes, obesity, exercise intolerance and increased brown adipose tissue by 47% compared with wild type littermates (WT). However, less is known about its role in cardioprotection. Accordingly we examined the effects of chronic myocardial ischemia after 1 and 3 weeks of permanent coronary artery occlusion (CAO) in 3-4 month old RGS14 KO and their WT. Scar size after 3 weeks CAO, determined by histology, was decreased by 33±5% in RGS14 KO, which was only possible in the face of permanent CAO if angiogenesis/arteriogenesis developed in the RGS14 KO mice hearts. Indeed, both angiogenesis assessed by Ki 67 endothelial cell staining and arteriogenesis, assessed by Ki 67 arteriole staining, more than doubled compared with WT. This was associated with a 206±25.5% increase in VEGF in the RGS14 KO hearts compared with WT. We then examined the role of BAT by using a simulated BAT KO, i.e., BAT was transplanted from the RGS14 KO to WT. In the WT with BAT transplants VEGF was increased by 90%. Infarct size, assessed as the fraction of area at risk, was lower, p<0.05, in the BAT transplants (27±2.8%), compared with infarct size in RGS14 KO donors (44±1.9%), a value similar to that observed in WT without the BAT transplant (46±1.0%). Thus, brown adipose tissue appears to be a novel mechanism to induce both angiogenesis and arteriogenesis, resulting in vascular protection from ischemia.