Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Yun Cai; Beijian Zhang; Adilan Shalamu; Tingwen Gao; Junbo Ge

doi:10.21037/atm-22-2583

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Ann Transl Med. 2022 Jun;10(12):662. doi: 10.21037/atm-22-2583.

Authors

Yun Cai^#^{1

2

3

4}, Beijian Zhang^#^{1

2

3

4}, Adilan Shalamu^#^{1

2

3

4}, Tingwen Gao^{1

2

3

4}, Junbo Ge^{1

2

3

4}

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Shanghai Institute of Cardiovascular Diseases, Shanghai, China.
³ Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China.
⁴ Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China.

^# Contributed equally.

Abstract

Background: This study aimed to verify the effect of soluble guanylate cyclase (sGC) stimulator vericiguat on myocardial ischemia-reperfusion injury and explore its mechanism.

Methods: A myocardial ischemia-reperfusion injury model of mice was established and intravenous administration was performed 2 minutes before reperfusion. Triphenyltetrazolium chloride (TTC) staining and echocardiography were used to verify the effect of vericiguat on myocardial ischemia-reperfusion injury in the infarct area, and immunofluorescence was used to observe myocardial pathological changes at different time points after reperfusion. Quantitative proteomics was conducted to analysis the main differentially expressed proteins after drug intervention. The distribution of endothelial cells and sGC after myocardial ischemia-reperfusion injury in mice was observed by immunofluorescence. RNA sequencing of endothelial cells was used to search for differentially expressed molecules. Thioflavin-S staining was used to observe the effect of vericiguat on improving the nonrecurrence phenomenon and reducing the infarct size after reperfusion.

Results: The effect of the sGC stimulator vericiguat on myocardial ischemia-reperfusion injury was verified, and myocardial microcirculation significantly increased after drug intervention. Quantitative proteomics found that the protein expression of myocardial tissue in the ischemia-reperfusion area was not significantly different in the drug intervention group, except for increased adenosine triphosphate (ATP) activity. Vericiguat, nitroglycerin, and nitrite did not directly affect apoptosis or cell viability. RNA sequencing of human umbilical vein endothelial cells screened the upregulated antioxidant response.

Conclusions: SGC stimulator vericiguat ameliorated myocardial ischemia-reperfusion injury through indirect pathways of improving microcirculation.

Keywords: Nitric oxide (NO); cyclic guanosine monophosphate (cGMP); ischemia-reperfusion injury; oxidative stress.