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Heme oxygenase-1 Ameliorates Oxidative Stress-Induced Endothelial Senescence via Regulating Endothelial Nitric Oxide Synthase Activation and Coupling

Heme oxygenase-1 Ameliorates Oxidative Stress-Induced Endothelial Senescence via Regulating Endothelial Nitric Oxide Synthase Activation and Coupling

Wenwei Luo, Yu Wang, Hanwei Yang, Chunmei Dai, Huiling Hong, Jingyan Li, Zhiping Liu, Zhen Guo, Xinyi Chen, Ping He, Ziqing Li, Fang Li, Jianmin Jiang, Peiqing Liu, Zhuoming Li

Aging (Albany NY). 2018 Jul 24;10(7):1722-1744.

PMID: 30048241

Abstract:

Aim:
Premature senescence of vascular endothelial cells is a leading cause of various cardiovascular diseases. Therapies targeting endothelial senescence would have important clinical implications. The present study was aimed to evaluate the potential of heme oxygenase-1 (HO-1) as a therapeutic target for endothelial senescence.
Methods and results:
Upregulation of HO-1 by Hemin or adenovirus infection reversed H2O2-induced senescence in human umbilical vein endothelial cells (HUVECs); whereas depletion of HO-1 by siRNA or HO-1 inhibitor protoporphyrin IX zinc (II) (ZnPP) triggered HUVEC senescence. Mechanistically, overexpression of HO-1 enhanced the interaction between HO-1 and endothelial nitric oxide synthase (eNOS), and promoted the interaction between eNOS and its upstream kinase Akt, thus resulting in an enhancement of eNOS phosphorylation at Ser1177 and a subsequent increase of nitric oxide (NO) production. Moreover, HO-1 induction prevented the decrease of eNOS dimer/monomer ratio stimulated by H2O2 via its antioxidant properties. Contrarily, HO-1 silencing impaired eNOS phosphorylation and accelerated eNOS uncoupling. In vivo, Hemin treatment alleviated senescence of endothelial cells of the aorta from spontaneously hypertensive rats, through upregulating eNOS phosphorylation at Ser1177.
Conclusions:
HO-1 ameliorated endothelial senescence through enhancing eNOS activation and defending eNOS uncoupling, suggesting that HO-1 is a potential target for treating endothelial senescence.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP15442645-B	Protoporphyrin IX zinc(II)		15442-64-5	Price

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