Adipose tissue angiogenesis.

A review of adipose tissue angiogenesis includes the morphological and cytochemical development of adipose tissue vasculature and the concept of primitive fat organs. Spatial and temporal relationships between fetal vascular and fat cell development are discussed, including depot- and genetic-dependent arteriolar differentiation. The relationship between connective tissue deposition and elaboration of adipose tissue vasculature is discussed with respect to regulating adipocyte development in a depot-dependent manner. In vitro studies indicated that depot-dependent vascular traits may be attributable to intrinsic growth characteristics of adipose tissue endothelial cells. These studies indicate that adipogenesis may be regulated by factors that drive angiogenesis. Fundamental aspects of angiogenesis, including basement membrane breakdown, vasculogenesis, angiogenic remodeling, vessel stabilization, and vascular permeability were reviewed. Critical angiogenic factors include vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins (Ang), ephrins, matrix metalloproteinases, and the plasminogen enzymatic system. Vascular endothelial growth factor is the most critical factor because it initiates the formation of immature vessels and disruption of a single VEGF allele leads to embryonic lethality in mice. Expression of VEGF is influenced by hypoxia, insulin, growth factors, and several cytokines. Angiogenic factors secreted and/or produced by adipocytes or preadipocytes are discussed. Vascular endothelial growth factor expression and secretion by adipocytes is regulated by insulin and hypoxia, and is associated with adipose tissue accretion. Vascular endothelial growth factor accounts for most of the angiogenic activity of adipose tissue. The proposed role of leptin as an adipogenic factor is reviewed with respect to efficacy on various aspects of angiogenesis relative to other angiogenic factors. The VEGF and leptin genes are both hypoxia inducible, but potential links between VEGF and leptin gene expression have not been examined. Finally, several studies including a study of mice treated with antiangiogenic factors indicate that adipose tissue accretion can be controlled through the vasculature per se.