OEA Alleviates Apoptosis in Diabetic Rats with Myocardial Ischemia/reperfusion Injury by Regulating the PI3K/Akt Signaling Pathway Through Activation of TRPV1

Overview

Journal Front Pharmacol

Date 2022 Dec 1

PMID 36452230

Authors

Enhui Yao

Lili Luo

Chenxi Lin

Jing Wen

Yanglongfei Li

Tong Ren

Yujie Chen

Jinhua Huang

Xin Jin

Affiliations

Soon will be listed here.

Abstract

Reperfusion therapy after myocardial infarction may lead to myocardial injury, which can be complicated and exacerbated by diabetes. The existing therapeutic methods for myocardial ischemia-reperfusion injury (MIRI) in diabetic patients are not ideal. Oleoylethanolamide (OEA) has been found to have protective effects on diabetes and acute cerebral ischemia. This study aimed to determine whether OEA can alleviate MIRI in diabetic rats, and to explore the underlying mechanism. The model of diabetic rats with MIRI was established by blocking the left coronary artery for 30 min, followed by restoring blood flow stability for 120 min. The myocardial enzyme spectrum, area of MIRI, and expression levels of apoptosis-related proteins were detected. The results showed that OEA pretreatment could reduce myocardial infarction area, protect myocardial tissue structure, and reduce myocardial cell apoptosis in diabetic rats with MIRI. Meanwhile, the levels of creatine kinase (CK)-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were reduced, while superoxide dismutase (SOD) level was elevated. H9C2 cells were treated with high glucose and oxygen-glucose deprivation/reperfusion (OGD/R) to establish an model. Capsazepine (CPZ), an antagonist of transient receptor potential vanilloid subtype 1 (TRPV1), and LY294002, an inhibitor of PI3K, were used to treat H9C2 cells . Apoptosis level and the expression levels of apoptosis-related proteins were measured. It was found that OEA activated TRPV1 and the PI3K/Akt signaling pathway, downregulated the expression levels of apoptosis-related proteins (Bcl-2 and cleaved caspase-3), and ameliorated the apoptosis of H9C2 cells treated with high glucose and OGD/R. This study clarified that OEA, as a TRPV1 agonist, could reduce myocardial cell apoptosis by activating the PI3K/Akt signaling pathway in diabetic rats with MIRI. The findings may provide a theoretical basis for administration of OEA as a potential therapeutic agent into diabetic patients with MIRI.

Citing Articles

The link between ferroptosis and autophagy in myocardial ischemia/reperfusion injury: new directions for therapy.

Yang X, Wu H, Liu D, Zhou G, Zhang D, Yang Q J Cardiovasc Transl Res. 2025; .

PMID: 39885084 DOI: 10.1007/s12265-025-10590-6.

Liu-Shen-Wan inhibits PI3K/Akt and TRPV1 signaling alleviating bone cancer pain in rats.

Zhang H, Jiang J, Chen X, Zhu F, Fu F, Chen A Cancer Biol Ther. 2024; 25(1):2432098.

PMID: 39587385 PMC: 11601056. DOI: 10.1080/15384047.2024.2432098.

Identification of mitochondria-related gene biomarkers associated with immune infiltration in acute myocardial infarction.

Liu G, Wang M, Lv X, Guan Y, Li J, Xie J iScience. 2024; 27(7):110275.

PMID: 39040073 PMC: 11261152. DOI: 10.1016/j.isci.2024.110275.

LncRNA SNHG1 alleviates myocardial ischaemia-reperfusion injury by regulating the miR-137-3p/KLF4/TRPV1 axis.

Tang R, Li W, Lu Y, Wang X, Gao S ESC Heart Fail. 2024; 11(2):1009-1021.

PMID: 38234046 PMC: 10966264. DOI: 10.1002/ehf2.14660.

Metabolomic Profiling of Aqueous Humor from Pathological Myopia Patients with Choroidal Neovascularization.

Wei Q, Yu Z, Zhou X, Gong R, Jiang R, Xu G Metabolites. 2023; 13(8).

PMID: 37623844 PMC: 10456621. DOI: 10.3390/metabo13080900.

References

Mazzola C, Medalie J, Scherma M, Panlilio L, Solinas M, Tanda G . Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors. Learn Mem. 2009; 16(5):332-7. PMC: 2683005. DOI: 10.1101/lm.1145209. View

Miki T, Itoh T, Sunaga D, Miura T . Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning. Cardiovasc Diabetol. 2012; 11:67. PMC: 3461466. DOI: 10.1186/1475-2840-11-67. View

Ren T, Ma A, Zhuo R, Zhang H, Peng L, Jin X . Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in Type 2 Diabetic Model. J Pharmacol Exp Ther. 2020; 373(1):81-91. DOI: 10.1124/jpet.119.262675. View

Jiang X, Liu G, Lei H, Li Z, Feng Q, Huang W . Activation of transient receptor potential vanilloid 1 protects the heart against apoptosis in ischemia/reperfusion injury through upregulating the PI3K/Akt signaling pathway. Int J Mol Med. 2017; 41(3):1724-1730. DOI: 10.3892/ijmm.2017.3338. View

Huang M, Cheng G, Tan H, Qin R, Zou Y, Wang Y . Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors. Exp Neurol. 2017; 295:66-76. PMC: 5991616. DOI: 10.1016/j.expneurol.2017.05.001. View

Bowen K, Kris-Etherton P, Shearer G, West S, Reddivari L, Jones P . Oleic acid-derived oleoylethanolamide: A nutritional science perspective. Prog Lipid Res. 2017; 67:1-15. DOI: 10.1016/j.plipres.2017.04.001. View

Eefting F, Rensing B, Wigman J, Pannekoek W, Liu W, Cramer M . Role of apoptosis in reperfusion injury. Cardiovasc Res. 2004; 61(3):414-26. DOI: 10.1016/j.cardiores.2003.12.023. View

Naseroleslami M, Sharifi M, Rakhshan K, Mokhtari B, Aboutaleb N . Nesfatin-1 attenuates injury in a rat model of myocardial infarction by targeting autophagy, inflammation, and apoptosis. Arch Physiol Biochem. 2020; 129(1):122-130. DOI: 10.1080/13813455.2020.1802486. View

Zhao J, Zhao Y, Hu Y, Peng J . Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease. Cell Mol Biol Lett. 2021; 26(1):32. PMC: 8265056. DOI: 10.1186/s11658-021-00276-7. View

10.

Hill M, Miller G, Carrier E, Gorzalka B, Hillard C . Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 2009; 34(8):1257-62. PMC: 2716432. DOI: 10.1016/j.psyneuen.2009.03.013. View

11.

Godoy L, Farkouh M . Surgical vs percutaneous coronary revascularization in patients with diabetes following an acute coronary syndrome. J Diabetes. 2019; 11(7):610-612. DOI: 10.1111/1753-0407.12917. View

12.

Pandey R, Mousawy K, Nagarkatti M, Nagarkatti P . Endocannabinoids and immune regulation. Pharmacol Res. 2009; 60(2):85-92. PMC: 3044336. DOI: 10.1016/j.phrs.2009.03.019. View

13.

Zhou Y, Yang L, Ma A, Zhang X, Li W, Yang W . Orally administered oleoylethanolamide protects mice from focal cerebral ischemic injury by activating peroxisome proliferator-activated receptor α. Neuropharmacology. 2012; 63(2):242-9. DOI: 10.1016/j.neuropharm.2012.03.008. View

14.

Sumanovski L, Sieber C . Neurally-mediated vasodilatation in normal and portal hypertensive rats: role of nitric oxide and calcitonin gene-related peptide. J Hepatol. 1998; 28(6):1031-6. DOI: 10.1016/s0168-8278(98)80353-x. View

15.

Brady N, Hamacher-Brady A, Gottlieb R . Proapoptotic BCL-2 family members and mitochondrial dysfunction during ischemia/reperfusion injury, a study employing cardiac HL-1 cells and GFP biosensors. Biochim Biophys Acta. 2006; 1757(5-6):667-78. DOI: 10.1016/j.bbabio.2006.04.011. View

16.

Ebel D, Mullenheim J, Frassdorf J, Heinen A, Huhn R, Bohlen T . Effect of acute hyperglycaemia and diabetes mellitus with and without short-term insulin treatment on myocardial ischaemic late preconditioning in the rabbit heart in vivo. Pflugers Arch. 2003; 446(2):175-82. DOI: 10.1007/s00424-003-1051-x. View

17.

Lakota J . Molecular mechanism of ischemia - Reperfusion injury after myocardial infarction and its possible targeted treatment. Int J Cardiol. 2016; 220:571-2. DOI: 10.1016/j.ijcard.2016.06.309. View

18.

Zhai K, Liskova A, Kubatka P, Busselberg D . Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells. Int J Mol Sci. 2020; 21(11). PMC: 7312732. DOI: 10.3390/ijms21114177. View

19.

Cheng X, Hu J, Wang Y, Ye H, Li X, Gao Q . Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway. J Diabetes Res. 2018; 2018:3071959. PMC: 6196799. DOI: 10.1155/2018/3071959. View

20.

Yang L, Guo H, Li Y, Meng X, Yan L, Zhang D . Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways. Sci Rep. 2016; 6:34611. PMC: 5056375. DOI: 10.1038/srep34611. View