NADPH oxidases are in part responsible for increased cardiovascular superoxide production during aging

NADPH oxidases are in part responsible for increased cardiovascular superoxide production during aging
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DOI:
10.1016/j.freeradbiomed.2006.02.020
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发表时间:
2006-06-15
影响因子:
7.4
通讯作者:
Rochette, Luc
Rochette, Luc
中科院分区:
医学1区
文献类型:
--
作者:
Oudot, Alexandra;Martin, Caroline;Rochette, Luc

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我们研究的目的是在大鼠中检查心肌缺血恢复的年龄相关差异,并确定与心脏和血管氧化应激修饰的可能关系。对年轻(2个月)、成年(6个月)和老年(21个月)Wistar大鼠的离体灌注心脏进行缺血-再灌注序列。进行血管组织形态学分析和NADPH氧化酶研究。免疫组化法检测血管紧张素AT(1)受体的表达。在缺血前期,但也在缺血后,心肌功能参数的年龄相关性下降,并与活性氧释放增加。根据ESR、荧光显微镜和免疫组织化学,在老年性支气管炎中,NADPH氧化酶的活性和表达随年龄增加而增加;涉及的NADPH氧化酶定位于内皮细胞。我们发现内皮血管紧张素AT的表达与年龄相关。我们的研究表明,心肌功能和适应缺血再灌注下降,在老化过程中,与更高水平的氧化应激。内皮细胞NADPH氧化酶是年龄相关性心血管恶化的主要原因。血管NADPH氧化酶活性的调节剂之一,肾素-血管紧张素系统,可能参与衰老过程中血管超氧化物产生的调节。(c)2006年爱思唯尔公司All rights reserved.
The aim of our study was to examine in rats, age-related differences in myocardial ischemic recovery and to determine the possible relationship with modification of cardiac and vascular oxidative stress. Isolated perfused hearts from young (2 months), adult (6 months), and old (21 months) Wistar rats were subjected to a ischemia-reperfusion sequence. Vascular histomorphological analyses were performed and NADPH oxidase was studied. The expression of angiotensin AT(1) receptors was evaluated using immumostaining. During the preischemic period, but also after ischemia, an aged-related decrease in myocardial functional parameters was observed, and was associated with an increased release of reactive oxygen species. In aortas, the activity and expression of NADPH oxidase increased with age according to the ESR, fluorescence microscopy, and immunohistochemistry; the NADPH oxidase involved was localized in endothelial cells. We found an age-related increase in the expression of endothelial angiotensin AT(1). Our study suggests that myocardial function and adaptation to ischemia-reperfusion declined during aging and are related to a higher level of oxidative stress. Endothelial NADPH oxidase is a major contributor to age-related cardiovascular deterioration. One of the regulators of vascular NADPH oxidase activity, the renin-angiotensin system, may be involved in the modulation of vascular superoxide production during the aging process. (c) 2006 Elsevier Inc. All rights reserved.