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(Circulation Research. 2005;97:850.)
© 2005 American Heart Association, Inc.

Editorials

NAD(P)H Oxidases and TGF-ß–Induced Cardiac Fibroblast Differentiation

Nox-4 Gets Smad

Petra Rocic, Pamela A. Lucchesi

From the Departments of Physiology (P.R.) and Pharmacology (P.A.L.), Louisiana State University Health Sciences Center, New Orleans, La.

Correspondence to Pamela A. Lucchesi, Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Skip Bertman Dr, Rm 2530, Baton Rouge, LA 70803. E-mail plucch@lsuhsc.edu

See related article, pages 900–907

Key Words: NAD(P)H oxidase • cardiac fibrosis • myofibroblasts • collagen

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Under normal conditions, cardiac fibroblasts play a pivotal role in the maintenance of the structural integrity of the myocardium by regulating extracellular matrix (ECM) production. In response to myocardial infarction and pressure overload, paracrine and autocrine signals in the interstitial milieu stimulate fibroblast proliferation and differentiation into myofibroblasts. The phenotype of these cells is characterized by an upregulation of smooth muscle -actin (SM -actin), collagen gel contraction in vitro, increased proliferation, decreased secretion of matrix degrading enzymes (matrix metalloproteinases), and enhanced production of extracellular matrix proteins, plasminogen activator inhibitor-1, and tissue inhibitors of matrix metalloproteineases. Thus, fibroblast transformation into myofibroblasts is associated with enhanced matrix production and decreased matrix turnover, resulting in interstitial fibrosis. This adverse ECM structural remodeling facilitates abnormalities of both systolic and diastolic cardiac function, because fibrosis leads to increase in chamber stiffness.¹

The renin–angiotensin system and transforming growth factor-ß1 (TGF-ß1) play a critical role in the development of cardiac fibrosis. Angiotensin II (Ang II)–dependent upregulation of TGF-ß1 expression in cardiac fibroblasts is absolutely required for Ang II–induced fibrosis.² TGF-ß1 induces the proliferation of cardiac fibroblasts, their phenotypic conversion to myofibroblasts, deposition of ECM proteins such as collagen, fibronectin, and proteoglycans, and hypertrophic growth of cardiomyocytes, thereby mediating Ang II–induced structural remodeling of the ventricular wall in an autocrine/paracrine manner.² The profibrotic effects of TGF-ß1 are primarily attributable to the differentiation of fibroblasts to myofibroblasts, because acute exposure (<24 hours) of primary rat cardiac fibroblasts fails to increase collagen production.³ On the other hand, chronic exposure to . . . [Full Text of this Article]

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