Heme oxygenase-1 inhibits angiotensin II-induced cardiac hypertrophy in vitro and in vivo
Heme oxygenase-1 inhibits angiotensin II-induced cardiac hypertrophy in vitro and in vivo
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DOI：
10.1161/01.cir.0000135475.35758.23
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发表时间：
2004-07-20
期刊：
影响因子：
37.8
通讯作者：
Chau, LY
中科院分区：
文献类型：
--
作者：
Hu, CM;Chen, YH;Chau, LY
血红素加氧酶-1（HO-1）是一种应激反应酶，参与心脏保护。探讨HO-1是否有心脏重塑反应的作用，其过度表达对血管紧张素II（Ang II）诱导的心脏hematopoiety.Methods和Results-HO-1诱导培养的新生大鼠心肌细胞治疗钴原卟啉IX（CoPPIX）或携带人HO-1基因的重组腺病毒。血管紧张素II诱导的心肌细胞肥大的细胞大小，[H-3]亮氨酸的摄取，和蛋白质含量的增量进行评估，抑制HO-1过表达。与锡原卟啉IX，HO抑制剂，共处理的细胞，显着逆转HO-1的抑制作用。胆红素是HO-1降解血红素的副产物之一，通过抑制Ang II诱导的活性氧产生介导了抑制作用，如2 '，7'-二氯荧光素探针所检测到的。HO-1的抗肥大作用在接受慢性Ang II输注的大鼠中也得到证实。CoPPIX共处理的动物显着衰减血管紧张素II诱导的左心室肥大和高动力性收缩，而伴随治疗锡原卟啉IX废除CoPPIX介导的cardioprotectioninvivo. Conclusions-HO-1衰减血管紧张素II诱导的心脏肥大在体外和体内，和胆红素介导，至少部分，HO-1通过抑制Ang II刺激后活性氧产生的抗肥大作用。
Background-Heme oxygenase-1 (HO-1) is a stress-response enzyme implicated in cardioprotection. To explore whether HO-1 has a role in cardiac remodeling response, the effect of its overexpression on angiotensin II (Ang II)-induced cardiac hypertrophy was examined.Methods and Results-HO-1 was induced in cultured rat neonatal cardiomyocytes by treatment with cobalt protoporphyrin IX (CoPPIX) or a recombinant adenovirus carrying the human HO-1 gene. Ang II-induced myocyte hypertrophy assessed by increments in cell size, [H-3]leucine uptake, and protein content was suppressed by HO-1 overexpression. Cotreatment of cells with tin protoporphyrin IX, a HO inhibitor, significantly reversed the suppressive effect of HO-1. Bilirubin, one of the byproducts of heme degradation by HO-1, mediated the suppressive effect through the inhibition of Ang II-induced production of reactive oxygen species, as detected by a 2', 7'-dichlorofluorescein probe. The antihypertrophic effect of HO-1 was also demonstrated in rats receiving chronic Ang II infusions. Cotreatment of animals with CoPPIX significantly attenuated Ang II-induced left ventricular hypertrophy and hyperdynamic contractions, whereas concomitant treatment with tin protoporphyrin IX abolished CoPPIX-mediated cardioprotection in vivo.Conclusions-HO-1 attenuates Ang II-induced cardiac hypertrophy both in vitro and in vivo, and bilirubin mediates, at least in part, the antihypertrophic effect of HO-1 via inhibition of reactive oxygen species production after Ang II stimulation.