Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning.
Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning.
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肥厚预处理中能量代谢的变化先于心脏结构和功能的改变
DOI：
10.3389/fcvm.2020.602100
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发表时间：
2020
影响因子：
3.6
通讯作者：
Zou Y
中科院分区：
文献类型：
--
作者：
Wu J;Lu J;Huang J;You J;Ding Z;Ma L;Dai F;Xu R;Li X;Yin P;Zhao G;Wang S;Yuan J;Yang X;Ge J;Zou Y
最近的研究表明，心肌肥厚预适应（HP）是由短期主动脉横缩（TAC）的脱带（De-TAC）产生的，可以保护心脏免受随后再收缩（Re-TAC）引起的肥厚反应。虽然心脏底物代谢在心力衰竭中受损，但hp驱动的能量学在心脏肥厚发展中的作用尚不清楚。在这里，我们研究了不同负荷条件下的能量代谢、心脏肥厚和功能，以及它们在HP中的关系。雄性C57BL/6J小鼠（10-12周龄）随机接受Sham、HP [TAC 3天（TAC 3d），主动脉脱带4天（De-TAC 4d），再主动脉复带4周（Re-TAC 4W）]和TAC （TAC 4周不脱带）治疗。利用心脏超声心动图、血流动力学和组织学评估心脏重塑和功能。实时荧光定量PCR检测胎儿基因（ANP、BNP）、葡萄糖代谢相关基因（glut4、pdk4）、脂肪酸氧化相关基因（mcad、pgc1α、mcd、pparα） mRNA表达水平。western blot检测肥厚调节因子ERK1/2、代谢应激激酶amp活化蛋白激酶（AMPK）及其下游靶点乙酰辅酶a羧化酶（ACC）的激活情况。与TAC 4W小鼠相比，Re-TAC 4W小鼠的葡萄糖和脂肪酸代谢损伤较小，心肌肥厚和功能障碍较少。此外，TAC 3d和De-TAC 4d组与Sham组相比，心肌肥大、纤维化和心功能均无显著差异。而glut4、pdk4、mcad、pgc1α、mcd、pparα均降低，AMPK、ACC在TAC 3d激活，De-TAC 4d恢复到Sham水平，提示HP小鼠心肌能量代谢的变化早于心脏结构和功能的变化。总的来说，HP改善了能量代谢，延缓了心脏重塑，强调了早期代谢改善对心脏肥厚的结构和功能恢复的潜在有益作用。
Recent studies have unveiled that myocardial hypertrophic preconditioning (HP), which is produced by de-banding (De-TAC) of short-term transverse aortic constriction (TAC), protects the heart against hypertrophic responses caused by subsequent re-constriction (Re-TAC) in mice. Although cardiac substrate metabolism is impaired in heart failure, it remains unclear about the role of HP-driven energetics in the development of cardiac hypertrophy. Here, we investigated energy metabolism, cardiac hypertrophy, and function following variational loading conditions, as well as their relationships in HP. Male C57BL/6J mice (10–12 weeks old) were randomly subjected to Sham, HP [TAC for 3days (TAC 3d), de-banding the aorta for 4 days (De-TAC 4d), and then re-banding the aorta for 4 weeks (Re-TAC 4W)], and TAC (TAC for 4 weeks without de-banding). Cardiac echocardiography, hemodynamics, and histology were utilized to evaluate cardiac remodeling and function. The mRNA expression levels of fetal genes (ANP and BNP), glucose metabolism-related genes (glut4, pdk4), and fatty acid oxidation-related genes (mcad, pgc1α, mcd, pparα) were quantitated by real-time quantitative PCR. Activation of hypertrophy regulators ERK1/2, a metabolic stress kinase AMP-activated protein kinase (AMPK), and its downstream target acetyl-coA carboxylase (ACC) were explored by western blot. Compared with TAC 4W mice, Re-TAC 4W mice showed less impairment in glucose and fatty acid metabolism, as well as less cardiac hypertrophy and dysfunction. Moreover, no significant difference was found in myocardial hypertrophy, fibrosis, and cardiac function in TAC 3d and De-TAC 4d groups compared with Sham group. However, glut4, pdk4, mcad, pgc1α, mcd, and pparα were all decreased, while AMPK and ACC were activated in TAC 3d and returned to Sham level in De-TAC 4d, suggesting that the change in myocardial energy metabolism in HP mice was earlier than that in cardiac structure and function. Collectively, HP improves energy metabolism and delays cardiac remodeling, highlighting that early metabolic improvements drive a potential beneficial effect on structural and functional restoration in cardiac hypertrophy.