Fibrous Tissue and Angiotensin II

Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in injured systemic organs such as the heart. Cultured myoFb, obtained from rat cardiac scar tissue, express genes that encode components requisite for angiotensin (Ang) II generation, which in turn regulates myoFb collagen tu...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1997-08, Vol.29 (8), p.2001-2012
Main Authors: Sun, Yao, Ramires, Felix J.A., Zhou, Guoping, Ganjam, Venkataseshu K., Weber, Karl T.
Format: Article
Language:English
Subjects:
Actins - analysis
Angiotensin converting enzyme
Angiotensin II - physiology
Angiotensin II receptor
Angiotensin Receptor Antagonists
Animals
Collagen - analysis
Connective Tissue - physiopathology
Croton Oil
Fibroblasts - metabolism
Fibroblasts - pathology
Granuloma - physiopathology
Hydroxyproline - analysis
Imidazoles - pharmacology
Lisinopril - pharmacology
Losartan - pharmacology
Macrophages - pathology
Male
Myofibroblasts
Peptidyl-Dipeptidase A - metabolism
Pouch tissue
Pyridines - pharmacology
Rat
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin - metabolism
Wound Healing - physiology
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Summary:Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in injured systemic organs such as the heart. Cultured myoFb, obtained from rat cardiac scar tissue, express genes that encode components requisite for angiotensin (Ang) II generation, which in turn regulates myoFb collagen turnover in an autocrine/paracrine manner. In this study, we tested the hypothesis that these wound-healing fibroblast-like cells and locally generated Ang II are involved in other repairing tissue. To test this hypothesis, we used a granuloma pouch model, where a subcutaneous air sac is created followed by injection of croton oil. Pouch tissue was collected at days 4, 7, 14 and 21. The presence of myoFb was determined by immunohistochemical α-smooth muscle actin (α-SMA) labeling and collagen accumulation by picrosirius red staining. Angiotensin converting enzyme (ACE) and Ang II receptor binding were detected byin vitroquantitative autoradiography using125I-351A and125I[Sar1, Ile8]Ang II, respectively, while Ang II receptor subtype was defined by displacement studies using either an AT1(losartan) or AT2(PD123177) receptor antagonist. Cells expressing ACE were determined by immunohistochemistry. Ang II content in pouch tissue was measured by radioimmunoassay following HPLC separation while its capacity to generate Ang II was assessed in tissue bath, with and without exogenous Ang I or lisinopril, an ACE inhibitor. Collagen accumulation in pouch tissue was examined by determining hydroxyproline content in response to lisinopril, AT1or AT2receptor antagonists (losartan or PD123177). In pouch tissue, we found: (1) myoFb at day 4 which became more extensive at days 7, 14 and 21; (2) morphologic evidence of collagen deposition evident at day 4, which gradually became more extensive thereafter; (3) ACE and Ang II receptor binding was evident at day 4 and remained invariant on days 7, 14 and 21; (4) the predominant Ang II receptor subtype expressed was AT1; (5) myoFb express ACE and AT1receptors; (6) picogram quantities of Ang II (per g tissue) was evident on days 7, 14 and 21; and (7) Ang II was generated from Ang I substrate. Lisinopril and losartan, but not PD123177, significantly attenuated pouch weight and accumulation of collagen. Thus, in this model of cutaneous repair, the appearance of myoFb is associated with Ang II generation that regulates fibrogenesis by AT1receptor binding. Signals involved in the appearance of myoFb remain uncertain. Further studies are re
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1997.0451