Consiglio Nazionale delle Ricerche (CNR), Institute of Clinical Physiology, Laboratory of Cardiovascular Biochemistry, Pisa, Italy.
Cardiovasc Diabetol. 2012 Nov 19;11:143. doi: 10.1186/1475-2840-11-143.
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.
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.
全身性和心肌脂联素(ADN)在扩张型心肌病中的作用仍存在争议。我们在非缺血性扩张型心肌病的猪模型中检测了全身性和心肌 ADN 的调节及其与 AMP 激活蛋白激酶(AMPK)活性的关系。
通过对左心室(LV)游离壁进行起搏(180 次/分,3 周),从起搏(PS)和对侧部位(OS)以及 5 个对照猪中采集了 7 只仪器化成年雄性小型猪的心脏组织。循环 ADN 水平与整体和局部心脏功能呈负相关。与对照相比,PS 中的心肌 ADN 下调(p < 0.05),但 ADN 受体 1 显著上调(p < 0.05)。在衰竭心脏的任何区域均未观察到 AMPK 的修饰。同样,与对照相比,心肌 PPARγ、PPARα、TNFα、iNOS 的 mRNA 水平没有变化。
矛盾的是,循环 ADN 并没有显示出任何心脏保护作用,这证实了它作为心力衰竭不良预后生物标志物的作用。与对照相比,PS 中的心肌 ADN 减少,但与 AMPK 无关,这表明在心脏 ADN 水平降低的情况下,可能会发生新的机制,从而导致心脏功能的局部下降。