Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload.
Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload.
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DOI：
10.1016/j.redox.2018.05.016
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发表时间：
2018-07
期刊：
影响因子：
11.4
通讯作者：
Hill BG
中科院分区：
文献类型：
--
作者：
Dassanayaka S;Zheng Y;Gibb AA;Cummins TD;McNally LA;Brittian KR;Jagatheesan G;Audam TN;Long BW;Brainard RE;Jones SP;Hill BG
心力衰竭期间的病理性心脏重构与脂质过氧化产物水平升高和几种醛解毒酶（包括醛脱氢酶2 (ALDH2)）丰度降低有关。一种新兴的观点可以解释这些发现，即亲电物种在氧化还原信号中的作用，这可能对应激或损伤的适应性反应很重要。本研究的目的是确定基因上增加ALDH2活性是否影响压力超载引起的心功能障碍。经主动脉横缩（TAC）治疗12周的小鼠出现心肌肥大和心功能障碍，这与ALDH2表达和活性降低有关。小鼠心脏特异性表达人ALDH2基因可增强心肌ALDH2活性，但不能改善压力过载时的心功能。TAC 12周后，ALDH2转基因小鼠的心脏比野生型小鼠更大，毛细血管密度更低。这些发现表明，ALDH2的过表达增强了对压力过载的肥厚反应，并暗示ALDH2的下调可能是对某些形式的心脏病理的适应性反应。压力超载引起的心力衰竭与ALDH2丰度和活性降低有关。我们产生了心肌细胞特异性，ALDH2过表达的小鼠，以抵消心力衰竭期间ALDH2的抑制。增加心脏ALDH2的表达并没有减轻压力超载引起的心功能障碍。ALDH2过表达增强了压力超载引起的肥厚。ALDH2过表达促进压力过载后毛细血管稀疏。
Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2). An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC) for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Pressure overload-induced heart failure is associated with lower ALDH2 abundance and activity. We generated a cardiomyocyte-specific, ALDH2-overexpressing mouse to offset the suppression of ALDH2 during heart failure. Augmenting expression of cardiac ALDH2 did not attenuate pressure overload-induced cardiac dysfunction. ALDH2 overexpression augmented pressure overload-induced hypertrophy. ALDH2 overexpression promoted capillary rarefaction following pressure overload.
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影响因子：
9.3
作者：
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通讯作者：
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DOI：
10.1152/ajpheart.00245.2004
发表时间：
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影响因子：
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