Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity.
The biological role of macrophage infiltration into adipose tissue in obesity remains to be fully understood. 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 suggest 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. Macrophages were found to be a major source of PDGF in adipose tissue, as deletion of macrophages led to a significant reduction in PDGF mRNA. In cell culture, PDGF expression was induced by hypoxia, and tube formation of endothelial cells 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 the PDGF level is elevated in adipose tissue, its activity in angiogenesis is dependent on the availability of sufficient endothelial cells. The study suggests a new function of macrophages in the adipose tissue in obesity.
Pang
Can
C
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
Gao
Zhanguo
Z
Yin
Jun
J
Zhang
Jin
J
Jia
Weiping
W
Ye
Jianping
J
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology; D009765:Obesity / Q000276:immunology / Q000473:pathology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D000943:Antigens, Differentiation; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D011494:Protein Kinases; D012333:RNA, Messenger; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C036763:monocyte-macrophage differentiation antigen; C546843:mTOR protein, mouse