Novel H2 S-NO hybrid molecule (ZYZ-803) promoted synergistic effects against heart failure

Redox Biology
Dan WuYi Zhun Zhu

Abstract

Therapeutic strategies that increase hydrogen sulfide (H2S) or nitric oxide (NO) are cytoprotective in various models of cardiovascular injury. However, the nature of interaction between H2S and NO in heart failure and the underlying mechanisms for the protective effects remain undefined. The present study tested the cardioprotective effect of ZYZ-803, a novel synthetic H2S-NO hybrid molecule that decomposed to release H2S and NO. ZYZ-803 dose dependently improved left ventricular remodeling and preserved left ventricular function in the setting of isoprenaline-induced heart failure. The cardioprotective effect of ZYZ-803 is significantly more potent than that of H2S and/or NO donor alone. ZYZ-803 stimulated the expression of cystathionine γ-lyase (CSE) for H2S generation and the activity of endothelial NO synthase (eNOS) for NO production. Blocking CSE and/or eNOS suppressed ZYZ-803-induced H2S and NO production and cardioprotection. ZYZ-803 increased vascular endothelial growth factor (VEGF) concentration and cyclic guanosine 5'-monophosphate (cGMP) level. Moreover, ZYZ-803 upregulated the endogenous antioxidants, glutathione peroxidase (GPx) and heme oxygenase 1 (HO-1). These findings indicate that H2S and NO cooperatively a...Continue Reading

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Citations

Feb 18, 2020·Oxidative Medicine and Cellular Longevity·Se Chan KangSung Ryul Lee
Oct 3, 2018·Oxidative Medicine and Cellular Longevity·Dan WuDeqiu Zhu
Nov 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peter RoseYi-Zhun Zhu
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Wei-Lu WangYi-Zhun Zhu
Apr 4, 2021·Antioxidants·Angela CorvinoBeatrice Severino
Apr 21, 2021·Cardiovascular & Hematological Disorders Drug Targets·Arkady R Kolpakov, Roman A Knyazev

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Methods Mentioned

BETA
pharmacotherapies
Assay
ELISA

Software Mentioned

Prism Graph

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