Ace2 Overexpression Inhibits Hypoxia-induced Collagen Production By Cardiac Fibroblasts

Title

Ace2 Overexpression Inhibits Hypoxia-induced Collagen Production By Cardiac Fibroblasts

Creator

Grobe J L; Der Sarkissian S; Stewart J M; Meszaros J G; Raizada M K; Katovich M J

Publisher

Clinical Science

Date

2007
2007-10

Description

Cardiac remodelling is a key risk factor for the development of heart failure in the chronic phase following myocardial infarction. Our previous studies have shown an anti-remodelling role of ACE2 (angiotensin-converting enzyme 2) in vivo during hypertension and that these protective effects are mediated through increased circulating levels of Ang-(1-7) [angiotensin-(1-7)]. In the present study, we have demonstrated that cardiac myocytes have modest ACE2 activity, whereas cardiac fibroblasts do not: exhibit any endogenous activity. As fibroblasts are the major cell type found in an infarct zone following a myocardial infarction, we examined the effects of ACE2 gene delivery to cultured cardiac fibroblasts after acute hypoxic exposure. Cardiac fibroblasts from 5-day-old Sprague-Dawley rat hearts were grown to confluence and transduced with a lentiviral vector containing murine ACE2 cDNA under transcriptional control by the EFI alpha (elongation factor I alpha) promoter (lenti-ACE2). Transduction of fibroblasts with lenti-ACE2 resulted in a viral dose-dependent increase in ACE2 activity. This was associated with a significant attenuation of both basal and hypoxia/re-oxygenation-induced collagen production by the fibroblasts. Cytokine production, specifically TGF beta (transforming growth factor beta), by these cells was also significantly attenuated by ACE2 expression. Collectively, these results indicate that: (i) endogenous ACE2 activity is observed in cardiac myocytes, but not in cardiac fibroblasts; (ii) ACE2 overexpression in the cardiac fibroblast attenuates collagen production; and (iii) this prevention is probably mediated by decreased expression of cytokines. We conclude that ACE2 expression, limited to cardiac fibroblasts, may represent a novel paradigm for in vivo therapy following acute ischaemia.

Subject

angiotensin-converting enzyme 2 (ACE2); angiotensin-converting enzyme-2; collagen; cross-talk; expression; fibroblast; growth-factor-beta; heart failure; hypoxia; Myocardial infarction; myofibroblast differentiation; oxidative stress; pathways; rat; remodelling; Research & Experimental Medicine; signaling; transforming growth factor beta (TGF beta)

Identifier

Format

Journal Article or Conference Abstract Publication

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

357-364

Issue

7

Volume

113

Citation

Grobe J L; Der Sarkissian S; Stewart J M; Meszaros J G; Raizada M K; Katovich M J, “Ace2 Overexpression Inhibits Hypoxia-induced Collagen Production By Cardiac Fibroblasts,” NEOMED Bibliography Database, accessed January 26, 2021, https://neomed.omeka.net/items/show/10014.

Social Bookmarking