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Distinct atrial and ventricular microRNA changes in experimental heart failure
Author(s) -
Chen Yu,
Wakili Reza,
Luo Xiaobin,
Naud Patrice,
Kaab Stefan,
Dobrev Dobromir,
Nattel Stanley
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1060.18
Subject(s) - heart failure , ventricle , medicine , microrna , fibrosis , extracellular matrix , ventricular remodeling , fibrillin , cardiac fibrosis , cardiology , fibronectin , chemistry , marfan syndrome , biology , microbiology and biotechnology , gene , biochemistry
Heart failure (HF) causes different forms of remodeling in left atrium (LA) vs left ventricle (LV), with fibrosis much more prominent in LA. MicroRNAs (miRs) are central regulators in cardiac remodeling. This study compared LA and LV miRNA changes during the development of experimental HF. Methods HF was induced in dogs by ventricular tachypacing (VTP, 240 bpm) for 0 (CTL), 12, 24 hrs, 1, 2 and 5 wks (n=5–8/group). MiR expression was assessed by microarray and qPCR. Results Microarrays showed greater changes in LA vs LV (Fig A). MiR‐29b, miR‐133a and miR‐30a decreased within 24 hrs; MiR‐21 and miR‐146b increases started at 1 wk only in LA (B, C). In contrast, miR‐214 and miR‐146a showed similar changes in LA and LV (D). MiR‐21, miR‐29b, miR‐133 and miR‐30 are implicated in extracellular‐matrix (ECM) remodeling. Collagen‐1/ ‐3, fibronectin 1 and fibrillin increased ~3.8–26‐fold*** to steady state at 1–2 wk, TIMP‐3 decreased from 24 hrs (~58%***) while MMP‐9 increased at 12 hrs (~9‐fold***) and remained elevated. Changes were much smaller in LV at all times, agreeing with atrial‐predominant fibrosis. miR‐214 and miR‐146 target I Ks and I Ca,L subunits, known to change in HF LA and LV. Conclusions VTP‐induced HF causes greater miRNA changes in LA vs LV. LA expression of miRs with effects on ECM synthesis, paralleled by related ECM expression changes, implicate miRNAs in HF related LA‐selective structural remodeling.