In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. 14 ( 2013-04-09), p. 1466-1475
Abstract:
Congestive heart failure (CHF) causes atrial fibrotic remodeling, a substrate for atrial fibrillation (AF) maintenance. MicroRNA29 (miR29) targets extracellular matrix proteins. In the present study, we examined miR29b changes in patients with AF and/or CHF and in a CHF-related AF animal model and assessed its potential role in controlling atrial fibrous tissue production. Methods and Results— Control dogs were compared with dogs subjected to ventricular tachypacing for 24 hours, 1 week, or 2 weeks to induce CHF. Atrial miR29b expression decreased within 24 hours in both whole atrial tissue and atrial fibroblasts (−87% and −92% versus control, respectively; p 〈 0.001 for both) and remained decreased throughout the time course. Expression of miR29b extracellular matrix target genes collagen-1A1 (COL1A1), collagen-3A1 (COL3A1), and fibrillin increased significantly in CHF fibroblasts. Lentivirus-mediated miR29b knockdown in canine atrial fibroblasts (−68%; p 〈 0.01) enhanced COL1A1, COL3A1, and fibrillin mRNA expression by 28% ( p 〈 0.01), 19% ( p 〈 0.05), and 20% ( p 〈 0.05), respectively, versus empty virus–infected fibroblasts and increased COL1A1 protein expression by 90% ( p 〈 0.05). In contrast, 3-fold overexpression of miR29b decreased COL1A1, COL3A1, and fibrillin mRNA by 65%, 62%, and 61% (all p 〈 0.001), respectively, versus scrambled control and decreased COL1A1 protein by 60% ( p 〈 0.05). MiR29b plasma levels were decreased in patients with CHF or AF (by 53% and 54%, respectively; both p 〈 0.001) and were further decreased in patients with both AF and CHF (by 84%; p 〈 0.001). MiR29b expression was also reduced in the atria of chronic AF patients (by 54% versus sinus rhythm; p 〈 0.05). Adenoassociated viral–mediated knockdown of miR29b in mice significantly increased atrial COL1A1 mRNA expression and cardiac tissue collagen content. Conclusions— MiR29 likely plays a role in atrial fibrotic remodeling and may have value as a biomarker and/or therapeutic target.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/CIRCULATIONAHA.112.001207
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2013
detail.hit.zdb_id:
1466401-X
