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Angiotensin II type 1 receptor signalling regulates microRNA differentially in cardiac fibroblasts and myocytes

Pia Lindgren Jeppesen1, Gitte Lund Christensen, Mikael Schneider

  • 1Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark and Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense, Denmark.

British Journal of Pharmacology
|April 1, 2011
PubMed
Abstract

Insights

Angiotensin II type 1 receptor (AT1R) signals regulate specific microRNAs (miRNAs) through Gαq/11-dependent pathways. These findings shed light on miRNA involvement in cardiovascular disease.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • MicroRNA Biology

Background:

  • The angiotensin II type 1 receptor (AT1R) plays a critical role in regulating blood pressure and cardiac function.
  • AT1R signaling is implicated in the pathogenesis of cardiac diseases.
  • MicroRNAs (miRNAs) are increasingly recognized for their involvement in cardiovascular conditions.

Purpose of the Study:

  • To investigate whether AT1R signaling influences miRNA expression.
  • To determine if AT1R-mediated miRNA regulation occurs via Gαq/11-dependent or -independent pathways.

Main Methods:

  • Global miRNA array analysis was performed on HEK293N cells overexpressing AT1R treated with angiotensin II (Ang II).
  • Experiments were designed to differentiate between Gαq/11-dependent and -independent signaling pathways.
  • Quantitative PCR was used to validate miRNA regulation in HEK293N cells and primary cardiac cells (myocytes and fibroblasts).

Main Results:

  • Ang II up-regulated five specific miRNAs (miR-29b, -129-3p, -132, -132*, and -212) in HEK293N cells.
  • A biased Ang II analogue selectively activating Gαq/11-independent signaling did not regulate these miRNAs.
  • Ang II-induced miRNA regulation was dependent on Gαq/11 and Mek1, and confirmed in cardiac fibroblasts; Ang II did not affect miRNA in cardiac myocytes, but a Gαq/11-independent analogue down-regulated miR-129-3p.

Conclusions:

  • Five miRNAs are regulated by Ang II through Gαq/11 and Erk1/2-dependent mechanisms.
  • These identified miRNAs may contribute to Ang II-mediated cardiac biology and disease.
  • The findings highlight the role of specific miRNAs in cardiovascular regulation and disease, with observed regulation in cardiac cells.

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