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

Tianwei Cui,Weiyu Liu,Chenghao Yu,Xiaolu Shi,Qiuyan Li,Jianxun Ren,Yikui Li,Jinyan Zhang

doi:10.3389/fphar.2021.752244

Abstract

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.

Highlights

Acute myocardial infarction (AMI) is a condition with high morbidity and mortality (McAloon et al, 2016)
LVID s was significantly greater in the model group than in the sham group (Figure 1A), whereas the values of LVAW s, LVAW d, ejection fraction (EF), fractional shortening (FS), and stroke volume (SV) were significantly lower in the model group than in the sham group
Our findings indicated that allicin significantly inhibited caffeineinduced coronary artery contractions, suggesting that allicininduced vasodilation of coronary arteries was associated with inhibition of the sarcoplasmic reticulum (SR) Ca2+ release mediated by ryanodine receptors (RyRs)

Summary

Introduction

Acute myocardial infarction (AMI) is a condition with high morbidity and mortality (McAloon et al, 2016). There is an urgent need to develop novel therapeutic strategies for preventing AMI. In this regard, traditional Chinese medicine (TCM) offers various advantages including the ability to target multiple biological pathways, low toxicity and costs, and fewer side effects (Liu et al, 2011). We previously demonstrated that allicin exerted anti-fibrotic and antiapoptotic effects in the myocardium, thereby ameliorating cardiac dysfunction in a rat model of AMI (Ma et al, 2017). We speculated that the anti-AMI effects of allicin might be related to the coronary vasomotor function and Ca2+ transport in cardiomyocytes

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Discussion

Conclusion