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Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure

Carine Cueille1, Elisabeth Pidoux, Marie-Christine de Vernejoul

  • 1INSERM-U349, Hôpital Lariboisière, Centre Viggo Petersen, 2 rue Ambroise Paré, 75475 Paris-Cedex 10, France.

Biochemical and Biophysical Research Communications
|June 8, 2002
PubMed

Insights

This study found that receptors for calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are upregulated in rat hearts with chronic heart failure. This suggests a compensatory role for these receptors in heart failure.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Receptor Biology

Background:

  • Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent vasodilators with potential roles in heart failure.
  • CGRP and ADM receptors are formed by the calcitonin receptor-like receptor (CRLR) associating with receptor activity-modifying proteins (RAMPs).
  • CRLR/RAMP1 forms a CGRP receptor, while CRLR/RAMP2 or CRLR/RAMP3 forms an ADM receptor.

Purpose of the Study:

  • To investigate the expression of CGRP and ADM receptors in a rat model of chronic heart failure.
  • To determine if receptor activity-modifying proteins (RAMPs) are upregulated in failing hearts.

Main Methods:

  • Utilized semi-quantitative RT-PCR to detect mRNA levels of RAMP1, RAMP3, CRLR, RAMP2, RDC1, and ADM.
  • Employed Western-blot analysis to quantify protein levels of RAMP1 and RAMP3.
  • Examined both atrial and ventricular tissues from rats subjected to aortic banding for 6 months.

Main Results:

  • Demonstrated a significant upregulation of RAMP1 and RAMP3 mRNA and protein in failing rat hearts.
  • Observed no changes in the expression of CRLR, RAMP2, RDC1, or ADM mRNA.
  • Found increased RAMP1 expression in both atria and ventricles, and increased RAMP3 expression in atria.

Conclusions:

  • Chronic heart failure in rats leads to an upregulation of CGRP receptors (via RAMP1) and ADM receptors (via RAMP3).
  • These findings suggest a compensatory mechanism involving CGRP and ADM signaling pathways in the failing heart.
  • The study provides evidence for a functional role of CGRP and ADM receptors in mitigating chronic heart failure in rats.

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