Submitted on March 14, 2008
Revised on April 22, 2008
Accepted on May 13, 2008
Macrophage Infiltration into Adipose Tissue May Promote Angiogenesis for Adipose Tissue Remodeling in Obesity
Can Pang, Zhanguo Gao1, Jun Yin2, Jin Zhang, Weiping Jia, and Jianping Ye3*
1 PBRC
2 Pennington Biomedical Research Center/LSU
3 Pennington Biomedical Research Center
* To whom correspondence should be addressed. E-mail: yej{at}pbrc.edu.
The biological role of macrophage infiltration into adipose tissue remains to be fully understood in obesity. We hypothesize that macrophages may act to stimulate angiogenesis in the adipose tissue. This possibility was examined by determining macrophage expression of angiogenic factor PDGF (platelet-derived growth factor) and regulation of tube formation of endothelial cells by PDGF. The data suggests that endothelial cell density was reduced in the adipose tissue of ob/ob mice. Expression of endothelial marker CD31 was decreased in protein and mRNA. The reduction was associated with an increase in macrophage infiltration. In the obese mice, PDGF concentration was elevated in the plasma, and its mRNA expression was increased in adipose tissue. Macrophage was found to be a major source of PDGF in adipose tissue as deletion of macrophage led to a significant reduction in PDGF mRNA. In cell culture, the PDGF expression was induced by hypoxia, and the tube formation of endothelial cell was induced by PDGF. The PDGF activity was dependent on S6K as inhibition of S6K in endothelial cells led to inhibition of the PDGF activity. We conclude that in response to the reduced vascular density, macrophages may express PDGF in adipose tissue to facilitate capillary formation in obesity. Although PDGF level is elevated in adipose tissue, its activity in angiogenesis is dependent on availability of sufficient endothelial cells. The study suggests a new function of macrophage in the adipose tissue in obesity.
