Diabetic angiopathy and angiogenic defects

Abstract

Diabetes is one of the most serious health problems in the world. A major complication of diabetes is blood vessel disease, termed angiopathy, which is characterized by abnormal angiogenesis. In this review, we focus on angiogenesis abnormalities in diabetic complications and discuss its benefits and drawbacks as a therapeutic target for diabetic vascular complications. Additionally, we discuss glucose metabolism defects that are associated with abnormal angiogenesis in atypical diabetic complications such as cancer.

Figure 1

Schematic image of angiogenesis switch. Angiogenesis results from the balanced functions of pro-angiogenic and anti-angiogenic molecules. Defects in the angiogenic balance lead to a shift toward either excessive angiogenesis or anti-angiogenesis. CSF, colony-stimulating factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; FLT1, fms-related tyrosine kinase 1; HGF, hepatocyte growth factor; IGF, insulin-like growth factor; MMP, matrixmetalloproteinases, PDGF, platelet-derived growth factor; PECAM-1, platelet endothelial cell adhesion molecular (also known as CD31); PEDF, pigment epithelium-derived factor; TGFβ, transforming growth factor-β; TIMP, tissue inhibitor of metalloproteinases; TNFa, tumor necrosis factor-α; VE, vascular endothelial; VEGF, vascular endothelial growth factor.

Figure 2

sFllt1 plays as endogenous inhibitor of VEGF signaling by trapping free-VEGF. VEGF signaling is strictly regulated by endogenous molecules, including sFlt1. sFlt1 binds to and sequesters VEGF from cell-surface VEGF receptors, subsequently VEGF modulated pro-angiogenesis signal is inhibited.

Figure 3

The biology of angiogenesis abnormality in diabetic organ dysfunction. In diabetes, the angiogenesis signal is regulated in an organ-, tissue-, and cell type-specific manner. In the retina, atherosclerotic plaque, kidney glomerulus, and cancer, VEGF likely plays pro-angiogenic roles; on the contrary, in diabetic heart, kidney tubule, peripheral vessels, and placenta, VEGF signal is inhibited.