Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress.
Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress.
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DOI：
10.1111/jcmm.12541
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发表时间：
2015-07
影响因子：
5.3
通讯作者：
Zhou S
中科院分区：
文献类型：
--
作者：
Huang J;Xu L;Huang Q;Luo J;Liu P;Chen S;Yuan X;Lu Y;Wang P;Zhou S
本研究旨在探讨脂肪酸β-氧化关键酶短链酰基辅酶A脱氢酶(SCAD)在大鼠心脏发育过程中的表达情况以及病理性和生理性心肌肥厚时SCAD的差异。 SCAD在胎儿和新生儿心脏中表达最低，在正常心脏发育过程中呈时间依赖性增加。相反，在不同年龄的自发性高血压大鼠（SHR）中观察到 SCAD 表达显着降低。另一方面，经过游泳训练的大鼠出现了生理性心脏肥大，而SHR则出现了病理性心脏肥大。两种心脏肥大在心肌脂肪酸利用方面表现出不同的 SCAD 变化。此外，病理性心肌细胞肥大时SCAD表达显着降低，而生理性心肌细胞肥大时SCAD表达升高。 SCAD siRNA治疗引发了病理性心肌细胞肥大，这表明SCAD表达下调可能在病理性心肌肥厚中发挥重要作用。过氧化物酶体增殖物激活受体α（PPARα）的变化与SCAD的变化一致。此外，特异性PPARα配体非诺贝特治疗可增加SCAD的表达并抑制病理性心脏肥大。因此，我们推测病理性心脏肥大中SCAD表达下调可能是“胎儿能量代谢重现”的原因。 PPARα 失活可能导致病理性心脏肥大中 SCAD 表达减少。病理性和生理性心肌肥厚的SCAD变化有所不同，可作为病理性和生理性心肌肥厚的分子标志物。
This study was designed to investigate the expression of short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid β-oxidation, during rat heart development and the difference of SCAD between pathological and physiological cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal heart, which had time-dependent increase during normal heart development. In contrast, a significant decrease in SCAD expression was observed in different ages of spontaneously hypertensive rats (SHR). On the other hand, swim-trained rats developed physiological cardiac hypertrophy, whereas SHR developed pathological cardiac hypertrophy. The two kinds of cardiac hypertrophy exhibited divergent SCAD changes in myocardial fatty acids utilization. In addition, the expression of SCAD was significantly decreased in pathological cardiomyocyte hypertrophy, however, increased in physiological cardiomyocyte hypertrophy. SCAD siRNA treatment triggered the pathological cardiomyocyte hypertrophy, which showed that the down-regulation of SCAD expression may play an important role in pathological cardiac hypertrophy. The changes in peroxisome proliferator-activated receptor α (PPARα) was accordant with that of SCAD. Moreover, the specific PPARα ligand fenofibrate treatment increased the expression of SCAD and inhibited pathological cardiac hypertrophy. Therefore, we speculate that the down-regulated expression of SCAD in pathological cardiac hypertrophy may be responsible for ‘the recapitulation of foetal energy metabolism’. The deactivation of PPARα may result in the decrease in SCAD expression in pathological cardiac hypertrophy. Changes in SCAD are different in pathological and physiological cardiac hypertrophy, which may be used as the molecular markers of pathological and physiological cardiac hypertrophy.