Key result
Rapid ventricular pacing reduces local myocardial adiponectin via an AMPK-independent pathway linked to cardiac dysfunction.
Why the study?
The role and regulation of systemic and myocardial adiponectin in dilated cardiomyopathy and its relationship with AMPK activity remain debated.
p-value: p=<0.05
In a non-ischemic heart failure model, regional reductions in myocardial adiponectin occur independent of AMPK signaling, suggesting novel local mechanisms of functional decline.
Should not alter clinical pacing or HF management; leaves open regional adiponectin as a translational target in non-ischemic models.
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.
No takes yet. Share an insight, caveat, or question.
Caselli et al. (2012) studied Dilated cardiomyopathy (swine model) (n=12). Left ventricular free wall pacing vs. Unpaced controls was evaluated on Myocardial adiponectin (ADN) expression and AMP-activated protein kinase (AMPK) activity (p=<0.05). Myocardial adiponectin was reduced in the pacing site compared to controls in an AMPK-independent fashion, suggesting regional down-regulation mediates the decline of cardiac function.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: