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Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury.
Exp Cell Res. 2021 01 15; 398(2):112389.EC

Abstract

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

Authors+Show Affiliations

Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China.Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, PR China. Electronic address: 37274036@qq.com.Department of Geriatrics and Cardiovascular Medicine, ShenZhen Hospital, Fuwai Hospital China Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital), Shenzhen, 518112, PR China. Electronic address: xhchen66@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33221316

Citation

Luo, Ying, et al. "Activation of the CaR-CSE/H2S Pathway Confers Cardioprotection Against Ischemia-reperfusion Injury." Experimental Cell Research, vol. 398, no. 2, 2021, p. 112389.
Luo Y, Liu LM, Xie L, et al. Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury. Exp Cell Res. 2021;398(2):112389.
Luo, Y., Liu, L. M., Xie, L., Zhao, H. L., Lu, Y. K., Wu, B. Q., Wu, Z. Y., Zhang, Z. L., Hao, Y. L., Ou, W. H., Liu, R. S., Xu, W. M., & Chen, X. H. (2021). Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury. Experimental Cell Research, 398(2), 112389. https://doi.org/10.1016/j.yexcr.2020.112389
Luo Y, et al. Activation of the CaR-CSE/H2S Pathway Confers Cardioprotection Against Ischemia-reperfusion Injury. Exp Cell Res. 2021 01 15;398(2):112389. PubMed PMID: 33221316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury. AU - Luo,Ying, AU - Liu,Li-Mei, AU - Xie,Li, AU - Zhao,Hong-Lei, AU - Lu,Yong-Kang, AU - Wu,Bao-Quan, AU - Wu,Zhi-Ye, AU - Zhang,Zhi-Ling, AU - Hao,Yun-Ling, AU - Ou,Wu-Hua, AU - Liu,Rui-Shuang, AU - Xu,Wen-Min, AU - Chen,Xie-Hui, Y1 - 2020/11/19/ PY - 2020/08/06/received PY - 2020/10/27/revised PY - 2020/11/17/accepted PY - 2020/11/23/pubmed PY - 2021/5/1/medline PY - 2020/11/22/entrez KW - Apoptosis KW - CaR-CSE/H2S pathway KW - Ischemia-reperfusion injury KW - Oxidative stress injury SP - 112389 EP - 112389 JF - Experimental cell research JO - Exp Cell Res VL - 398 IS - 2 N2 - Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury. SN - 1090-2422 UR - https://www.unboundmedicine.com/medline/citation/33221316/Activation_of_the_CaR_CSE/H2S_pathway_confers_cardioprotection_against_ischemia_reperfusion_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(20)30642-X DB - PRIME DP - Unbound Medicine ER -