Chen Chang, Huo Rong, Tong Yan, Sheng Yue, Liu Hui-Bin, Gao Xu, Nakajima Osamu, Yang Bao-Feng, Dong De-Li
Department of Pharmacology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, PR China.
Cell Physiol Biochem. 2011;28(1):25-32. doi: 10.1159/000331710. Epub 2011 Aug 16.
BACKGROUND/AIMS: Heme oxygenase-1(HO-1) has been reported to protect against cardiac hypertrophy in cultured neonatal cardiomyocytes treated with HO-1 inducer, cardiac specific HO-1 transgenic mice, or animals treated with HO-1 inducer. The aim of the present study is to examine the effects of systemic HO-1 transgenic overexpression on pressure overload-induced cardiac hypertrophy in mice.
Pressure-overload cardiac hypertrophy was induced by transverse aortic constriction (TAC) in WT (wild type) and systemic HO-1 transgenic overexpression (TG) mice.
We found that systemic HO-1 transgenic overexpression aggravated pressure overload-induced cardiac hypertrophy. Pressure-overload induced the more increases of heart weight/ body weigh index, left ventricular weight/ body weight index, β-MHC protein expression, cardiac interstitial fibrosis in TG mice than in WT mice. Pressure-overload increased cardiac HO-1 protein expression in WT but not TG mice, but the cardiac HO-1 protein level was still higher in TAC-treated TG mice than in TAC-treated WT mice. The basal cardiac calcineurin protein level in TG mice was lower than that in WT mice. Pressure-overload increased calcineurin protein expression in both WT and TG mice; however, pressure-overload induced more calcineurin protein expression in TG mice than in WT mice.
This study shows for the first time that systemic HO-1 transgenic overexpression aggravates pressure overload-induced cardiac hypertrophy.
背景/目的：据报道，血红素加氧酶-1（HO-1）在用HO-1诱导剂处理的培养新生心肌细胞、心脏特异性HO-1转基因小鼠或用HO-1诱导剂处理的动物中，可预防心脏肥大。本研究的目的是检测全身HO-1转基因过表达对小鼠压力超负荷诱导的心脏肥大的影响。
通过横断主动脉缩窄（TAC）在野生型（WT）小鼠和全身HO-1转基因过表达（TG）小鼠中诱导压力超负荷性心脏肥大。
我们发现全身HO-1转基因过表达加重了压力超负荷诱导的心脏肥大。与WT小鼠相比，压力超负荷诱导TG小鼠的心脏重量/体重指数、左心室重量/体重指数、β-肌球蛋白重链（β-MHC）蛋白表达、心脏间质纤维化增加得更多。压力超负荷使WT小鼠而非TG小鼠的心脏HO-1蛋白表达增加，但在TAC处理的TG小鼠中，心脏HO-1蛋白水平仍高于TAC处理的WT小鼠。TG小鼠基础心脏钙调神经磷酸酶蛋白水平低于WT小鼠。压力超负荷使WT小鼠和TG小鼠的钙调神经磷酸酶蛋白表达均增加；然而，压力超负荷诱导TG小鼠的钙调神经磷酸酶蛋白表达比WT小鼠更多。
本研究首次表明全身HO-1转基因过表达加重了压力超负荷诱导的心脏肥大。
