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Resveratrol pretreatment alleviates myocardial ischemia/reperfusion injury by inhibiting STIM1-mediated intracellular calcium accumulation

  • Han Xu
  • Jing Cheng
  • Xianbao Wang
  • Haiqiong Liu
  • Siyi Wang
  • Jixiong Wu
  • Banglong Xu
  • Aihua ChenEmail author
  • Fei HeEmail author
Original Article

Abstract

Previous studies have shown that stromal interaction molecule1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) contributes to intracellular Ca2+ accumulation in H9C2 cells subjected to hypoxia/reoxygenation(H/R) injury. The aim of the present study was to investigate the effect of resveratrol on STIM1-mediated intracellular Ca2+ accumulation and subsequent cell death in the context of myocardial ischemia/reperfusion (I/R) injury. C57 BL/6 mice were fed with either saline or resveratrol (50 mg/kg daily for 2 weeks) and then subjected to myocardial I/R injury. TTC/Evans Blue staining and TUNEL assay were performed to quantify the infarct size and apoptosis index. The cardiac function was evaluated by echocardiography. Neonatal rat ventricular cardiomyocytes (NRVCs) underwent hypoxia/reoxygenation (H/R) to establish the in vitro model. To achieve over-expression, NRVCs were transfected with STIM1-adenovirus vector. Apoptosis was analyzed by TUNEL assay. Cell viability was measured using MTS assay and cell necrosis was determined by LDH release assay. Intracellular Ca2+ concentration was detected by laser scanning confocal microscopy using a Fluo-3AM probe. Resveratrol significantly reduced apoptosis, decreased infarct size, and improved cardiac function in mice subjected to myocardial I/R injury. In NRVCs, resveratrol also downregulated STIM1 expression accompanied by decreased intracellular Ca2+ accumulation elicited by H/R injury. In addition, resveratrol reduced cell apoptosis, upregulated the Bcl-2, decreased Bax, and cleaved caspase-3 expression. Furthermore, the effects of resveratrol on STIM1-mediated intracellular Ca2+ accumulation, apoptotic proteins, and H/R-induced cell injury were exacerbated by STIM1 over-expression and were partly abolished by SOCE inhibitor SKF96365 in NRVCs in vitro. Our findings demonstrate that resveratrol exerts anti-apoptotic activity and improves cardiac functional recovery following myocardial I/R by inhibiting STIM1-induced intracellular Ca2+ accumulation.

Keywords

Resveratrol Ischemia reperfusion injury STIM1 Calcium Apoptosis 

Abbreviations

AAR

Area at risk

PCI

Percutaneous coronary intervention

NCX

Na+-Ca2+ exchanger

ACS

Acute coronary syndrome

AMI

Acute myocardial infarction

STEMI

ST segment elevation myocardial infarction

SOCE

Store-operated calcium channels

STIM

stromal interaction molecule

RSV

Trans-3,4′,5-trihydroxystilbene

I/R

Ischemia/reperfusion

DMEM

Dulbecco’s modified Eagle’s medium

FBS

Fetal bovine serum

Notes

Funding information

This work was supported by the Anhui Provincial Natural Science Foundation (grant no. 1808085QH235 to He Fei), Youth Elites Support Plan in universities of Anhui Province (grant no. gxyq2019013 to He Fei), Science and Technology New Star Program of Second affiliated Hospital of Anhui Medical University (grant no. 2018KA06 to He Fei), Key Natural Science Project of Anhui Colleges and Universities (grant no. KJ2018A0284 to Cheng Jing), Natural Science Foundation of China (grant no. 81903833 to Cheng Jing), and Natural Science Foundation of China (grant no. 81873460 to Chen Aihua).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© University of Navarra 2019

Authors and Affiliations

  1. 1.Department of CardiologySecond Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Clinical Medical College of Anhui Medical UniversityHefeiChina
  3. 3.School of NursingAnhui University of Traditional Chinese MedicineHefeiChina
  4. 4.Department of Cardiology, Heart Center, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  5. 5.Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular DiseaseGuangzhouChina
  6. 6.Sino-Japanese Cooperation Platform for Translational Research in Heart FailureGuangzhouChina
  7. 7.Laboratory of Heart Center, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina

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