Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model
1 Consiglio Nazionale delle Ricerche (CNR), Institute of Clinical Physiology, Laboratory of Cardiovascular Biochemistry, Pisa, Italy
2 Department of Medicine, Scuola Superiore Sant’Anna, Pisa, Italy
3 Fondazione CNR-Regione Toscana “G. Monasterio”, Pisa, Italy
4 Department of Experimental Pathology BMIE, Faculty of Medicine, University of Pisa, Pisa, Italy
5 Human Section of Histology and Medical Embryology, Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy
Cardiovascular Diabetology 2012, 11:143 doi:10.1186/1475-2840-11-143Published: 19 November 2012
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.
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.