Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive rats
Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive rats
复制标题
DOI：
10.1002/pmic.200500337
复制
发表时间：
2006-03-01
期刊：
影响因子：
3.4
通讯作者：
Fang, NY
中科院分区：
文献类型：
--
作者：
Jin, X;Xia, L;Fang, NY
虽然高血压患者的心脏肥厚已经得到了很好的认识，但肥厚发生的分子机制仍然很大程度上是未知的。本研究采用2-DE联合MALDI-TOF/TOF MS/MS对不同年龄自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）左心室心肌蛋白表达谱进行分析。结果表明，肥厚心肌中有20种蛋白被调节。在这些被调节的蛋白中，13种蛋白在持续高血压发生前的早期SHR中出现显著变化，而其他7种蛋白的表达变化仅发生在血压显著升高的SHR晚期，并且通过肾素-血管紧张素-醛固酮系统抑制剂氯沙坦或依那普利治疗在很大程度上是可逆的。这些数据表明，在肥厚的心脏中，能量代谢的变化有利于糖酵解的增加和脂肪酸和葡萄糖氧化的减少，这发生在没有高血压的SHR的早期阶段。我们的研究结果也提供了证据支持氧化应激在高血压性心脏肥厚的发展中起重要作用的假设。
Although cardiac hypertrophy in hypertension has been well recognized, the molecular mechanisms for the development of hypertrophy are still largely unknown. in this study, the protein expression profiles of left ventricular myocardia in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at different ages were analyzed using 2-DE in combination with MALDI-TOF/TOF MS/MS. The results showed that 20 proteins were modulated in the hypertrophic myocardium. Out of these modulated proteins, 13 proteins presented significant changes in SHR at an early stage prior to the development of sustained hypertension, while the changes of the other 7 protein expressions occurred only at a late stage in SHR when the blood pressure was significantly elevated, and were largely reversible by treatment with rennin-angiotensin-aldosterone system inhibitors losartan or enalapril. These data demonstrate that the changes in energy metabolism in the hypertrophied heart favor an increase in glycolysis and a decrease in oxidation of fatty acid and glucose, which occur at an early stage in SHR without hypertension. Our results also provide evidence to support the hypothesis that oxidative stress plays an important role in the development of hypertensive cardiac hypertrophy.