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 cells 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 models of kidney damage, renal RAS activation, cell proliferation, and upregulation of growth factors and matrix production were described. In some of these models, blockade of Ang II actions by ACE inhibitors and angiotensin type 1 (AT(1)) antagonists prevents proteinuria, gene expression upregulation, and fibrosis, as well as inflammatory cell infiltration. Interestingly, Ang II could also be involved in the fibrotic process because of its behavior as a proinflammatory cytokine, participating in various steps of the inflammatory response: Ang II (1) activates mononuclear cells and (2) increases proinflammatory mediators (cytokines, chemokines, adhesion molecules, nuclear factor kappaB). Finally, Ang II also regulates matrix degradation. These data show that drugs controlling this complex vasoactive peptide are probably one of the best ways of avoiding fibrosis in progressive renal diseases.
Mezzano
S A
SA
Division of Nephrology School of Medicine, Universidad Austral, Valdivia, Chile.
Ruiz-Ortega
M
M
Egido
J
J
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II