Angiotensin II and renal fibrosis

Angiotensin (Ang) II, the main peptide of the renin angiotensin system (RAS ), is a renal growth factor, inducing hyperplasia/hypertrophy depending on the cell type. This vasoactive peptide activates mesangial and tubular cell s and interstitial fibroblasts, increasing the expression and synthesis of extracellular matrix proteins. Some of these effects seem to be mediated by the release of other growth factors, such as TGF-beta. In experimental mod els of kidney damage, renal RAS activation, cell proliferation, and upregul ation of growth factors and matrix production were described. In some of th ese models, blockade of Ang II actions by ACE inhibitors and angiotensin ty pe 1 (AT(1)) antagonists prevents proteinuria, gene expression upregulation , and fibrosis, as well as inflammatory cell infiltration. Interestingly, A ng II could also be involved in the fibrotic process because of its behavio r as a proinflammatory cytokine, participating in various steps of the infl ammatory response: Ang II (1) activates mononuclear cells and (2) increases proinflammatory mediators (cytokines, chemokines, adhesion molecules, nucl ear factor kappaB). Finally, Ang II also regulates matrix degradation. Thes e data show that drugs controlling this complex vasoactive peptide are prob ably one of the best ways of avoiding fibrosis in progressive renal disease s.