Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury

Luo, Ying; Liu, Limei; Xie, Li; Zhao, Hulin; Lu, Yongkang; Wu, Bao-Quan; Wu, Zhimin; Zhang, Zhiling; Hao, Yanbin; Ou, Wu-Hua; Liu, Rui-Shuang; Xu, Wei; Chen, Xiehui

doi:10.1016/j.yexcr.2020.112389

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…In this study, we only evaluated the role of CSE, but not that of CBS or 3-MST; hence, this study cannot fully elucidate the role of each enzyme in the rat coronary artery. Our results showed that the CSE inhibitor inhibited allicin-induced vasodilation in coronary arteries by 42.4%, indicating that a considerable amount of CSE exists in rat coronary arteries, and that its role in inducing H 2 S production cannot be neglected, as previously suggested in some studies ( Chai et al, 2015 ; Luo et al, 2021 ). Regarding the controversy over the dominant role of each H 2 S-producing enzyme in coronary arteries, four reasons could explain such discrepancies.…”

Section: Discussionsupporting

confidence: 78%

Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport

Cui

Liu

et al. 2022

Front. Pharmacol.

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Acute myocardial infarction (AMI) is a condition with high morbidity and mortality, for which effective treatments are lacking. Allicin has been reported to exert therapeutic effects on AMI, but the underlying mechanisms of its action have not been fully elucidated. To investigate this, a rat model of AMI was generated by ligating the left anterior descending branch of the coronary artery. DL-propargylglycine (PAG), a specific hydrogen sulfide (H2S) synthetase inhibitor, was used to examine the effects of allicin on H2S production. Isolated coronary arteries and cardiomyocytes were assessed for vascular reactivity and cellular Ca2+ transport using a multiwire myography system and a cell-contraction-ion detection system, respectively. Allicin administration improved cardiac function and myocardial pathology, reduced myocardial enzyme levels, and increased H2S and H2S synthetase levels. Allicin administration resulted in concentration-dependent effects on coronary artery dilation, which were mediated by receptor-dependent Ca2+ channels, ATP-sensitive K+ channels, and sarcoplasmic reticulum (SR) Ca2+ release induced by the ryanodine receptor. Allicin administration improved Ca2+ homeostasis in cardiomyocytes by increasing cardiomyocyte contraction, Ca2+ transient amplitude, myofilament sensitivity, and SR Ca2+ content. Allicin also enhanced Ca2+ uptake via SR Ca2+-ATPase and Ca2+ removal via the Na+/Ca2+ exchanger, and it reduced SR Ca2+ leakage. Notably, the protective effects of allicin were partially attenuated by blockade of H2S production with PAG. Our findings provide novel evidence that allicin-induced production of H2S mediates coronary artery dilation and regulation of Ca2+ homeostasis in AMI. Our study presents a novel mechanistic insight into the anti-AMI effects of allicin and highlights the therapeutic potential of this compound.

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Section: Discussionsupporting

confidence: 78%

Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport

Cui

Liu

et al. 2022

Front. Pharmacol.

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“…For example, the activation of CaSR exerts a protective function against endothelial injury in ischemia or reperfusion injury by inhibiting platelet activation [67]. Addititonaly, it also offers protection to cardiac tissues against apoptosis and oxidative stress caused by this pathological condition [68]. On the other hand, CaSR phosphorylates PKCδ, which is known to regulate intracellular calcium levels [69] by translocating it to the ER resulting in ER related stress hormones to further inducing apoptosis in the vascular cells in-vivo [27].…”

Section: Myocardial Infarctionmentioning

confidence: 99%

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Sundararaman

Vorst

2021

IJMS

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The calcium Sensing Receptor (CaSR) is a cell surface receptor belonging to the family of G-protein coupled receptors. CaSR is mainly expressed by parathyroid glands, kidneys, bone, skin, adipose tissue, the gut, the nervous system, and the cardiovascular system. The receptor, as its name implies is involved in sensing calcium fluctuations in the extracellular matrix of cells, thereby having a major impact on the mineral homeostasis in humans. Besides calcium ions, the receptor is also activated by other di- and tri-valent cations, polypeptides, polyamines, antibiotics, calcilytics and calcimimetics, which upon binding induce intracellular signaling pathways. Recent studies have demonstrated that CaSR influences a wide variety of cells and processes that are involved in inflammation, the cardiovascular system, such as vascular calcification, atherosclerosis, myocardial infarction, hypertension, and obesity. Therefore, in this review, the current understanding of the role that CaSR plays in inflammation and its consequences on the cardiovascular system will be highlighted.

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“…H 2 S is generated mainly by cystathionine γ-lyase (CSE) in cardiovascular tissues [ 468 ]. In CSE knockout rats subjected to I/R injury, oxidative stress was aggravated, whereas increased expression of H 2 S and CSE in aortic tissues resulted in alleviation of oxidative stress accompanied by reduced expression of apoptosis-related proteins [ 471 ]. H 2 S produced by CSE improves contractile function in heart failure, and treatment with S -propyl- l -cysteine (SPRC) or sodium hydrosulfide (NaHS), modulators of blood H 2 S levels, attenuated the development of heart failure, reduced lipid peroxidation, and preserved mitochondrial function in mouse models [ 472 ].…”

Section: Sources and Actions Of Reactive Oxygen Speciesmentioning

confidence: 99%

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Heusch,

Andreadou,

Bell

et al. 2023

Redox Biology

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Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury

Cited by 5 publications

References 35 publications

Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport

Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

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