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Cultured Myofibroblasts Generate Angiotensin Peptidesde Novo

https://doi.org/10.1006/jmcc.1997.0376Get rights and content

Abstract

Scar tissue found at the site of myocardial infarction (MI) contains phenotypically transformed fibroblast-like cells termed myofibroblasts (myoFb). In injured cardiac tissue, autoradiography and immunolabeling have localized high density angiotensin (Ang) converting enzyme (ACE) and Ang II receptor binding to these cells, suggesting that they may regulate local concentrations of Ang II and transduce signals at this site. Ang II is known to modulate type I collagen gene expression of fibroblasts and myoFb, and to promote fibrous tissue contraction, each of which may contribute to tissue repair. It is unknown whether myoFb themselves generate Ang peptidesde novovia expression of angiotensinogen (Ao), an aspartyl protease needed to convert Ao to Ang I, and ACE. We therefore isolated and cultured myoFb from 4-week-old scar tissue of the adult rat left ventricle with transmural MI. In cultured myoFb we found: (a) immunoreactive membrane-bound ACE, cytosolic cathepsin D (Cat-D), and AT1receptors by immunofluorescence and confocal microscopy; (b) mRNA expression for Ao, ACE, and Cat-D, but not renin, by reverse transcriptase-polymerase chain reaction; (c) production of Ang I and II in serum-free culture media; (d) absence of renin activity; (e) a time-dependent conversion of Ao to Ang I by myoFb cytosol, which was inhibited by pepstatin A, but not by renin inhibitor; and (f ) significant increase in Ang II production (P<0.05) by exogenous Ao and Ang I (10 nm), which was significantly blocked by lisinopril (0.1μm;P<0.05). Thus, cultured myoFb express requisite components and are able to generate Ang I and IIde novo. In an autocrine and/or paracrine manner, Ang II may regulate myoFb collagen turnover and fibrous tissue contraction.

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Please address all correspondence to: Laxmansa C. Katwa, University of Missouri Health Sciences Center, Division of Cardiology, Rm. MA432 Medical Sciences Building, Columbia, MO 65212, USA.

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