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

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

Chiara Caselli  1 , Vincenzo Lionetti, Manuela Cabiati, Tommaso Prescimone, Giovanni D Aquaro, Virginia Ottaviano, Fabio Bernini, Letizia Mattii, Silvia Del Ry, Daniela Giannessi
Affiliations

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

Chiara Caselli et al. Cardiovasc Diabetol. .

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.

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Figures

Figure 1
Figure 1
ADN presence in both plasma and cardiac tissue. A) Circulating levels of ADN measured by Western Blotting before the beginning of the experimental protocol and after 21 days of pacing induction (n = 7); B) ADN expression at mRNA level from PS, OS and controls; C) relative blots of circulating levels of ADN (a); mRNA expression of ADN (b) as well as housekeeping genes, GAPDH (c), HPRT-1 (d), TBP (e) measured by RT-PCR and immunoblots of ADN by Western blot (f); D) representative immunostaining of ADN from heart sections showing the extra-cellular localization of ADN in peri-vascular tissue of PS.
Figure 2
Figure 2
ADN receptors in cardiac tissue from both PS and OS as well as in control hearts. A) relative blots of AdipoR1 (a), AdipoR2 (b) and T-cadherin (c) RT-PCR products; B) mRNA expression of Adipo R1; C) AdipoR2, and D) T-cadherin.
Figure 3
Figure 3
ADN regulation. A) mRNA expression of PPARγ and B) TNFα in PS, OS and controls C)as well as relative blots of RT-PCR products D); relationships between ADN and BNP mRNA expression; E) representative immunostaining of hematoxilin and eosin stain from heart sections.
Figure 4
Figure 4
Cardiac molecular pathways involved in ADN signaling. A) relative immunoblots of pAMPK and AMPK as well as mRNA expression of PPARα and iNOS; B) the ratio of phospho-AMPK and AMPK in PS, OS and controls; C) mRNA expression of PPARα; D) mRNA expression of iNOS; E) van Gieson’s staining of heart section from PS, OS and controls.
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