Stimulation of reactive oxygen species and collagen synthesis by angiotensin II in cardiac fibroblasts.
Superoxide anion generated by NAD(P)H-oxidase has an important role in the pathogenesis of cardiovascular diseases and scavenging superoxide anion can be considered as a reasonable therapeutic strategy. In hypertensive heart diseases there is a mutual reinforcement of reactive oxygen species (ROS) and angiotensin II (ANG II). ANG II increases the NAD(P)H-dependent superoxide anion production and the intracellular generation of ROS in cardiac fibroblasts and apocynin, a membrane NAD(P)H oxidase inhibitor, abrogates this rise. ANG II also stimulates the collagen production, the collagen I and III content and mRNA expression in cardiac fibroblasts and apocynin abolishes this induction. In this review we demonstrate that scavenging superoxide anion by tempol or EUK-8 or administration of PEG-superoxide dismutase (SOD) inhibits collagen production in cardiac fibroblasts. On the contrary increasing superoxide anion formation by inhibition of SOD stimulates collagen production. A vital role of SOD and the generated ROS can be suggested in the regulation and organization of collagen in cardiac fibroblasts. Specific pharmacological intervention with SOD mimetics can probably be an alternative approach for reducing myocardial fibrosis.
Lijnen
Paul J
PJ
Hypertension and Cardiovascular Rehabilitation Unit, Department of Cardiovascular Diseases, Katholieke Universiteit Leuven, Leuven, Belgium. paul.lijnen@med.kuleuven.be
van Pelt
Jos F
JF
Fagard
Robert H
RH
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis; D016166:Free Radical Scavengers / Q000494:pharmacology; D006331:Heart Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013481:Superoxides; D000804:Angiotensin II; D003094:Collagen; D019255:NADPH Oxidases