title: Angiotensin II in renal fibrosis: should TGF-beta rather than blood pressure be the therapeutic target?
abstract: A large body of data has now implicated elevations in the cytokine transforming growth factor-beta (TGF-beta) as a key mediator of tissue fibrosis. A number of mechanisms by which TGF-beta can be increased have been identified. Among them is the potent vasoconstrictor angiotensin II (ANG II). In vitro data indicate that ANG II, independent of blood pressure, increases synthesis and decreases degradation of pathological extracellular matrix components. These effects are largely, but not completely, mediated by ANG II induction of TGF-beta. In many models of renal fibrosis and in a number of human renal diseases, blockade of ANG II retards disease progression. Very recent studies indicate that ANG II blockade suppresses TGF-beta, whether the therapeutic agent is an angiotensin converting enzyme inhibitor or an ANG II type 1 receptor antagonist. These data suggest that an important antifibrotic, therapeutic effect of ANG II blockade is reduction of TGF-beta overexpression and raise the question of whether disease progression could be further retarded if ANG II blockade were optimized for maximal TGF-beta reduction rather than for normalization of systemic blood pressure.
authors.affiliation: Division of Nephrology, University of Utah School of Medicine, Salt Lake City 84132, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Noble
authors.forename: W A
authors.initials: WA
authors.lastname: Border
mesh_terms: D000804:Angiotensin II / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D016212:Transforming Growth Factor beta; D000804:Angiotensin II