Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis

Eva Van Rooij, Lillian B. Sutherland, Jeffrey E. Thatcher, J. Michael DiMaio, R. Haris Naseem, William S. Marshall, Joseph A Hill, Eric N Olson

Research output: Contribution to journalArticle

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Abstract

Acute myocardial infarction (MI) due to coronary artery occlusion is accompanied by a pathological remodeling response that includes hypertrophic cardiac growth and fibrosis, which impair cardiac contractility. Previously, we showed that cardiac hypertrophy and heart failure are accompanied by characteristic changes in the expression of a collection of specific microRNAs (miRNAs), which act as negative regulators of gene expression. Here, we show that MI in mice and humans also results in the dysregulation of specific miRNAs, which are similar to but distinct from those involved in hypertrophy and heart failure. Among the MI-regulated miRNAs are members of the miR-29 family, which are downregulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.

Original languageEnglish (US)
Pages (from-to)13027-13032
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number35
DOIs
StatePublished - Sep 2 2008

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MicroRNAs
Fibrosis
Myocardial Infarction
Collagen
Down-Regulation
Heart Failure
Messenger RNA
Elastin
Coronary Occlusion
Cardiomegaly
Regulator Genes
Hypertrophy
Coronary Vessels
Fibroblasts
Gene Expression
Growth
Proteins
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. / Van Rooij, Eva; Sutherland, Lillian B.; Thatcher, Jeffrey E.; DiMaio, J. Michael; Naseem, R. Haris; Marshall, William S.; Hill, Joseph A; Olson, Eric N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 35, 02.09.2008, p. 13027-13032.

Research output: Contribution to journalArticle

Van Rooij, Eva ; Sutherland, Lillian B. ; Thatcher, Jeffrey E. ; DiMaio, J. Michael ; Naseem, R. Haris ; Marshall, William S. ; Hill, Joseph A ; Olson, Eric N. / Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 35. pp. 13027-13032.
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