Niemann Bernd, Pan Ruping, Issa Hassan, Simm Andreas, Schulz Rainer, Rohrbach Susanne
Department of Cardiac and Vascular Surgery, University Hospital Giessen and Marburg, Justus Liebig University Giessen, 35392 Giessen, Germany.
Department of Cardiothoracic Surgery, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany.
Biology (Basel). 2022 Mar 16;11(3):448. doi: 10.3390/biology11030448.
Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury. Here, we investigated the role of AMP-activated protein kinase (AMPK) in mediating the cardioprotective CR effects in failing, postinfarct myocardium.
Ligation of the left coronary artery or sham operation was performed in rats and mice. Four weeks after surgery, left ventricular (LV) function was analyzed by echocardiography, and animals were assigned to different feeding groups (control diet or 40% CR, 8 weeks) as matched pairs. The role of AMPK was investigated with an AMPK inhibitor in rats or the use of alpha 2 AMPK knock-out mice.
CR resulted in a significant improvement in LV function, compared to postinfarct animals receiving control diet in both species. The improvement in LV function was accompanied by a reduction in serum BNP, decrease in LV proapoptotic activation, and increase in mitochondrial biogenesis in the LV. Inhibition or loss of AMPK prevented most of these changes.
The failing, postischemic heart is protected from progressive loss of LV systolic function by CR. AMPK activation is indispensable for these protective effects.
热量限制（CR）可延长包括哺乳动物在内的许多物种的寿命。CR通过纠正已存在的线粒体功能障碍和凋亡激活，对衰老心肌具有心脏保护作用。此外，它还能对急性缺血再灌注损伤起到心脏保护作用。在此，我们研究了AMP激活蛋白激酶（AMPK）在介导热量限制对梗死心肌功能衰竭的心脏保护作用中的作用。
对大鼠和小鼠进行左冠状动脉结扎或假手术。术后四周，通过超声心动图分析左心室（LV）功能，并将动物作为匹配对分配到不同的喂养组（对照饮食或40%热量限制，持续8周）。使用AMPK抑制剂在大鼠中或使用α2 AMPK基因敲除小鼠来研究AMPK的作用。
与两种物种中接受对照饮食的梗死动物相比，热量限制导致左心室功能显著改善。左心室功能的改善伴随着血清脑钠肽的降低、左心室促凋亡激活的减少以及左心室内线粒体生物合成的增加。AMPK的抑制或缺失阻止了这些变化中的大多数。
热量限制可保护缺血后心脏功能衰竭的心脏免于左心室收缩功能的逐渐丧失。AMPK激活对于这些保护作用是不可或缺的。
