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Humid heat exposure induced oxidative stress and apoptosis in cardiomyocytes through the angiotensin II signaling pathway

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Abstract

Exposure to humid heat stress leads to the initiation of serious physiological dysfunction that may result in heat-related diseases, including heat stroke, heat cramp, heat exhaustion, and even death. Increasing evidences have shown that the humid heat stress-induced dysfunction of the cardiovascular system was accompanied with severe cardiomyocyte injury; however, the precise mechanism of heat stress-induced injury of cardiomyocyte remains unknown. In the present study, we hypothesized that humid heat stress promoted oxidative stress through the activation of angiotensin II (Ang II) in cardiomyocytes. To test our hypothesis, we established mouse models of humid heat stress. Using the animal models, we found that Ang II levels in serum were significantly up-regulated and that the Ang II receptor AT1 was increased in cardiomyocytes. The antioxidant ability in plasma and heart tissues which was detected by the ferric reducing/antioxidant power assay was also decreased with the increased ROS production under humid heat stress, as was the expression of antioxidant genes (SOD2, HO-1, GPx). Furthermore, we demonstrated that the Ang II receptor antagonist, valsartan, effectively relieved oxidative stress, blocked Ang II signaling pathway and suppressed cardiomyocyte apoptosis induced by humid heat stress. In addition, overexpression of antioxidant genes reversed cardiomyocyte apoptosis induced by Ang II. Overall, these results implied that humid heat stress increased oxidative stress and caused apoptosis of cardiomyocytes through the Ang II signaling pathway. Thus, targeting the Ang II signaling pathway may provide a promising approach for the prevention and treatment of cardiovascular diseases caused by humid heat stress.

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Abbreviations

Ang II:

Angiotensin II

AOA:

Antioxidant ability

AT1:

Angiotensin receptor 1

ELISA:

Enzyme linked immunosorbent assay

FRAP:

The ferric reducing/antioxidant power assay

GPx:

Glutathione peroxidase

HHS:

Humid heat stress

HO-1:

Heme oxygenase 1

HRP:

Horseradish peroxidase

JNK:

c-Jun amino-terminal kinases

LDH:

Lactate dehydrogenase

MAPKs:

Mitogen-activated protein kinases

MDA:

Malondialdehyde

NAD(P)H:

Nicotinamide-adenine dinucleotide phosphate

qRT-PCR:

Quantitative real-time polymerase chain reaction

RAS:

Renin–angiotensin system

ROS:

Reactive oxygen species

RT:

Room temperature

SOD:

Superoxide dismutase

TBS:

Tris-buffered saline

TBST:

TBS and tween

TPTZ:

Tripyridyl-s-triazine

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Authors and Affiliations

  1. Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, 510010, China

    Xiaowu Wang, Binbin Yuan, Wenpeng Dong, Bo Yang, Yongchao Yang & Xi Lin

  2. Department of Anesthesiology, General Hospital of Chengdu Military Command, No. 270, Tianhui Road, Jinniu District, Chengdu, 610083, Si Chuang, People’s Republic of China

    Gu Gong

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  1. Xiaowu Wang
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  2. Binbin Yuan
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Correspondence to Gu Gong.

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Wang, X., Yuan, B., Dong, W. et al. Humid heat exposure induced oxidative stress and apoptosis in cardiomyocytes through the angiotensin II signaling pathway. Heart Vessels 30, 396–405 (2015). https://doi.org/10.1007/s00380-014-0523-6

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  • DOI: https://doi.org/10.1007/s00380-014-0523-6

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