All Title Author
Keywords Abstract


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

DOI: 10.1186/1475-2840-11-143

Keywords: Adiponectin receptors, Heart failure, Animal models, AMPK, Adiponectin

Full-Text   Cite this paper   Add to My Lib

Abstract:

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.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.Adiponectin (ADN) is an adipocyte-derived protein that is abundantly present in plasma [1] and is also expressed in cardiomyocytes [2] and endothelial cells [3]. Two ADN receptors, AdipoR1 and AdipoR2, have been characterized: AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver [4]. T-cadherin, an additional ADN receptor, is expressed in cardiomyocytes and is involved in ADN-mediated cardioprotection [5]. The remodeling of the failing heart has induced a number of investigators to test the hypothesis that modulation of myocardial metabolism might prove therapeutically advantageous [6].Potential downstream effectors of ADN receptors include AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPAR-α). AMPK is considered an energy-sensing enzyme that on stimulation enhances glucose use and fatty acid oxidation, whereas PPAR-α is a key nuclear transcription factor, regulating expression of genes involved in fatty acid upt

Full-Text

comments powered by Disqus