Angiogenesis and hypoxia in the kidney

作者：Tanaka Tetsuhiro; Nangaku Masaomi^*

来源：Nature Reviews Nephrology, 2013, 9(4): 211-222.

DOI：10.1038/nrneph.2013.35

Loss of glomerular function associated with the presence of tubulointerstitial lesions, which are characterized by peritubular capillary loss, is a common finding in progressive renal disorders. Dysregulated expression of angiogenic factors (such as vascular endothelial growth factor [VEGF] and angiopoietins) and endogenous angiogenic inhibitors (such as thrombospondin-1, angiostatin and endostatin) underlie these conditions and negatively influence the balance between capillary formation and regression, resulting in capillary rarefaction. Recent studies have provided unequivocal evidence for a pathogenic role of tubulointerstitial hypoxia and the involvement of hypoxia-inducible transcription factors in the advanced stages of chronic kidney disease. The mainstay of potential angiogenic therapies is the application of angiogenic factors with the primary aim of ameliorating reduced oxygenation in the ischaemic tubulointerstitium. However, this strategy is strongly associated with inflammation and changes in vascular permeability. For example, supraphysiological expression of VEGF results in glomerular expansion and proteinuria, whereas VEGF blockade using neutralizing antibodies can cause hypertension and thrombotic microangiopathy. These effects highlight the importance of tight regulation of angiogenic factors and inhibitors. Novel therapeutic approaches that target vascular maturation and normalization are now being developed to protect kidneys from capillary rarefaction and hypoxic injury. Tanaka, T. & Nangaku, M. Nat. Rev. Nephrol. 9, 211-222 (2013); published online 5 March 2013; doi:10.1038/nrneph.2013.35

• 出版日期2013-4