Cultured myofibroblasts generate angiotensin peptides de novo

Laxmansa C. Katwa, Scott E. Campbell, Suresh C. Tyagi, Soon Jin Lee, George T. Cicila, Karl Weber

Research output: Contribution to journalArticle

115 Citations (Scopus)

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 peptides de novo via 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 AT1 receptors 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 (0.1 μM; P < 0.05). Thus, cultured myoFb express requisite components and are able to generate Ang I and II de novo. In an autocrine and/or paracrine manner, Ang II may regulate myoFb collagen turnover and fibrous tissue contraction.

Original languageEnglish (US)
Pages (from-to)1375-1386
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number5
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Myofibroblasts
Angiotensins
Angiotensinogen
Angiotensin II
Angiotensin I
Peptides
Renin
Cathepsin D
Peptidyl-Dipeptidase A
Cicatrix
Fibroblasts
Myocardial Infarction
Aspartic Acid Proteases
Lisinopril
Angiotensin Receptors
Serum-Free Culture Media
Enzymes
Collagen Type I
Reverse Transcriptase Polymerase Chain Reaction
Autoradiography

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Cultured myofibroblasts generate angiotensin peptides de novo. / Katwa, Laxmansa C.; Campbell, Scott E.; Tyagi, Suresh C.; Lee, Soon Jin; Cicila, George T.; Weber, Karl.

In: Journal of Molecular and Cellular Cardiology, Vol. 29, No. 5, 01.01.1997, p. 1375-1386.

Research output: Contribution to journalArticle

Katwa, Laxmansa C. ; Campbell, Scott E. ; Tyagi, Suresh C. ; Lee, Soon Jin ; Cicila, George T. ; Weber, Karl. / Cultured myofibroblasts generate angiotensin peptides de novo. In: Journal of Molecular and Cellular Cardiology. 1997 ; Vol. 29, No. 5. pp. 1375-1386.
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