Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

Cardiovasc Diabetol. 2012 Nov 19:11:143. doi: 10.1186/1475-2840-11-143.

Abstract

Background: The role of systemic and myocardial adiponectin (ADN) in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK) activity in a swine model of non-ischemic dilated cardiomyopathy.

Methods and results: Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV) free wall (180 beats/min, 3 weeks), both from pacing (PS) and opposite sites (OS), and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p < 0.05), yet ADN receptor 1 was significantly up-regulated (p < 0.05). No modifications of AMPK were observed in either region of the failing heart. Similarly, myocardial mRNA levels of PPARγ, PPARα, TNFα, iNOS were unchanged compared to controls.

Conclusions: Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adiponectin / blood
  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Animals
  • Cardiac Pacing, Artificial
  • Cardiomyopathy, Dilated / blood
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / metabolism*
  • Cardiomyopathy, Dilated / physiopathology
  • Disease Models, Animal
  • Down-Regulation
  • Heart Failure / blood
  • Heart Failure / genetics
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Male
  • Myocardium / pathology*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Pilot Projects
  • RNA, Messenger / metabolism
  • Receptors, Adiponectin / metabolism
  • Stroke Volume
  • Swine
  • Swine, Miniature
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Ventricular Function, Left
  • Ventricular Remodeling

Substances

  • Adiponectin
  • PPAR alpha
  • PPAR gamma
  • RNA, Messenger
  • Receptors, Adiponectin
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • AMP-Activated Protein Kinases