Changes in short‐chain acyl‐coA dehydrogenase during rat cardiac development and stress

Abstract

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.

Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis

“…It had been reported that SCAD deficiency could be observed in pathological cardiomyocytes, but not in physiological cardiomyocytes (29). Additionally, this deficiency was closely related to the deactivation of peroxisome proliferator-activated receptor α (PPARα) (29). Up to now, we still could not find any hint to link the above-mentioned changes with ICH (Fig.…”

Effects of short‐chain acyl‐CoA dehydrogenase on cardiomyocyte apoptosis

“…siRNA‐1186, the most efficient small interference RNA (siRNA) for SCAD, was used for our experiments . The sequence of siRNA‐1186 were: sense 5′‐CCGCAUCACUGAGAUCAUTT‐3′ and antisense 5′‐AUAGAUCUCAGUGAU GCGGTT‐3′.…”

“…Our previous researches had revealed that SCAD expression was significantly down‐regulated in pathological cardiac hypertrophy in vivo and in vitro for the first time. Moreover, we also have found that pathological cardiac hypertrophy exhibited SCAD changes in myocardial fatty acids utilization . Nevertheless, the role of SCAD in cardiomyocyte apoptosis is currently still unknown.…”

“…It has been shown that AMPK activation inhibited cardiac hypertrophy through the reactivation of PPARα signalling pathway . Besides, we have previously shown that deactivation of PPARα led to the decrease in SCAD expression in pathological cardiac hypertrophy . However, the role of the AMPK/PPARα pathway in the prevention of cell apoptosis induced by acute oxidative stress remains unclear.…”

“…Peroxisome proliferator‐activated receptor‐α (PPARα), a member of fatty acid‐activated nuclear receptor family, was involved in the development of left ventrical hypertrophy and cardiomyocyte apoptosis . Previous studies have shown that SCAD gene was regulated by PPARα . AMP‐activated protein kinase (AMPK) is a crucial metabolic energy sensor and its activation has been reported to directly reflect with the heart against hypertrophy, ischaemic injury and cell death .…”