MicroRNA-34a Promotes Ischemia-Induced Cardiomyocytes Apoptosis Through Targeting Notch1

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2022 Mar 10

PMID 35265142

Authors

Jialin Pan

Lili Zhou

Cong Lin

Weihao Xue

Peng Chen

Jiafeng Lin

Affiliations

Soon will be listed here.

Abstract

Myocardial apoptosis occurs during myocardial ischemia. This study aimed to determine the effect of microRNA-34a (miR-34a) in ischemia-induced myocardial apoptosis. Mainly, SD rats were subjected to myocardial ischemia by ligaturing the left anterior descending branch of coronary artery. After rats had myocardial infarction, HE staining and TUNEL staining confirmed a significant increase in apoptosis. The expression of miR-34a was noticeably upregulated, while the expression of Notch1 was downregulated. An increase in caspase-3 and a decrease in Bcl-2/Bax ratio were observed in myocardium. Similar results were observed in the model of cardiomyocyte ischemia and anoxia of this study. When rat cardiomyocytes were administered with serum starvation and microaerophilic system, apoptosis-related proteins were significantly increased. However, transfecting the miR-34a inhibitor into the cardiomyocyte before the serum starvation and hypoxia treatment could increase the ratio of Bcl-2/Bax and downregulate the expression of caspase-3, as well as prevent cardiomyocytes from apoptosis. As opposed to the abovementioned points, the upregulation of miR-34a expression by transfecting miR-34a mimics induced Notch1 reduce and apoptosis-related proteins increase apparently, while upregulation of Notch1 could stimulate apoptosis attributed to miR-34a. Mechanistically, we demonstrated that Notch1 is a direct target of miR-34a. In conclusion, our current results suggested that miR-34a significantly stimulates ischemia-induced cardiomyocytes apoptosis by targeting Notch1.

Citing Articles

Dihydromyricetin Protects Against Hypoxia/Reoxygenation Injury in Cardiomyocytes by Activating miR-34a-Mediated Notch1 Pathway.

Li Y, Li M Cardiovasc Toxicol. 2025; 25(2):294-305.

PMID: 39864044 DOI: 10.1007/s12012-025-09959-5.

Adult zymosan re-exposure exacerbates the molecular alterations in the brainstem rostral ventromedial medulla of rats with early life zymosan-induced cystitis.

Talluri B, Addya S, Terashvili M, Medda B, Banerjee A, Shaker R Neurobiol Pain. 2024; 16:100160.

PMID: 39252992 PMC: 11381896. DOI: 10.1016/j.ynpai.2024.100160.

Mitochondrial complex-1 as a therapeutic target for cardiac diseases.

Rai N, Venugopal H, Rajesh R, Ancha P, Venkatesh S Mol Cell Biochem. 2024; 480(2):869-890.

PMID: 39033212 DOI: 10.1007/s11010-024-05074-1.

Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs.

Lee S Antioxidants (Basel). 2024; 13(6).

PMID: 38929095 PMC: 11200533. DOI: 10.3390/antiox13060656.

Unraveling Therapeutic Opportunities and the Diagnostic Potential of microRNAs for Human Lung Cancer.

Sweef O, Zaabout E, Bakheet A, Halawa M, Gad I, Akela M Pharmaceutics. 2023; 15(8).

PMID: 37631277 PMC: 10459057. DOI: 10.3390/pharmaceutics15082061.

References

Luxan G, DAmato G, MacGrogan D, de la Pompa J . Endocardial Notch Signaling in Cardiac Development and Disease. Circ Res. 2015; 118(1):e1-e18. DOI: 10.1161/CIRCRESAHA.115.305350. View

Simoons M, Windecker S . Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularization. Eur Heart J. 2010; 31(5):530-41. DOI: 10.1093/eurheartj/ehp605. View

Jia G, Wang Q, Wang R, Deng D, Xue L, Shao N . Tubeimoside-1 induces glioma apoptosis through regulation of Bax/Bcl-2 and the ROS/Cytochrome C/Caspase-3 pathway. Onco Targets Ther. 2015; 8:303-11. PMC: 4321652. DOI: 10.2147/OTT.S76063. View

Chen X, Li S, Zeng Z, Gu Z, Yu Y, Zheng F . Notch1 signalling inhibits apoptosis of human dental follicle stem cells via both the cytoplasmic mitochondrial pathway and nuclear transcription regulation. Int J Biochem Cell Biol. 2016; 82:18-27. DOI: 10.1016/j.biocel.2016.11.013. View

Mosaad S, Zaitone S, Ibrahim A, El-Baz A, Abo-Elmatty D, Moustafa Y . Celecoxib aggravates cardiac apoptosis in L-NAME-induced pressure overload model in rats: Immunohistochemical determination of cardiac caspase-3, Mcl-1, Bax and Bcl-2. Chem Biol Interact. 2017; 272:92-106. DOI: 10.1016/j.cbi.2017.05.012. View

Boon R, Dimmeler S . MicroRNAs in myocardial infarction. Nat Rev Cardiol. 2014; 12(3):135-42. DOI: 10.1038/nrcardio.2014.207. View

Bommer G, Gerin I, Feng Y, Kaczorowski A, Kuick R, Love R . p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007; 17(15):1298-307. DOI: 10.1016/j.cub.2007.06.068. View

Du M, Shan J, Feng A, Schmull S, Gu J, Xue S . Oestrogen Receptor β Activation Protects Against Myocardial Infarction via Notch1 Signalling. Cardiovasc Drugs Ther. 2020; 34(2):165-178. PMC: 7223456. DOI: 10.1007/s10557-020-06949-3. View

Patel A, Prabhakaran D, Berendsen M, Mohanan P, Huffman M . Pre-hospital policies for the care of patients with acute coronary syndromes in India: A policy document analysis. Indian Heart J. 2017; 69 Suppl 1:S12-S19. PMC: 5388021. DOI: 10.1016/j.ihj.2016.06.012. View

10.

Pan J, Zhang J, Zhang X, Zhou X, Lu S, Huang X . Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells. Int J Mol Med. 2014; 34(5):1381-7. DOI: 10.3892/ijmm.2014.1935. View

11.

Carthew R, Sontheimer E . Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009; 136(4):642-55. PMC: 2675692. DOI: 10.1016/j.cell.2009.01.035. View

12.

Roth G, Johnson C, Abajobir A, Abd-Allah F, Abera S, Abyu G . Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017; 70(1):1-25. PMC: 5491406. DOI: 10.1016/j.jacc.2017.04.052. View

13.

Zhang L, Wang L, Dong D, Wang Z, Ji W, Yu M . MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis. Cell Prolif. 2018; 52(1):e12527. PMC: 6430481. DOI: 10.1111/cpr.12527. View

14.

Liu L, Charville G, Cheung T, Yoo B, Santos P, Schroeder M . Impaired Notch Signaling Leads to a Decrease in p53 Activity and Mitotic Catastrophe in Aged Muscle Stem Cells. Cell Stem Cell. 2018; 23(4):544-556.e4. PMC: 6173623. DOI: 10.1016/j.stem.2018.08.019. View

15.

Wang X, Guo Z, Ding Z, Mehta J . Inflammation, Autophagy, and Apoptosis After Myocardial Infarction. J Am Heart Assoc. 2018; 7(9). PMC: 6015297. DOI: 10.1161/JAHA.117.008024. View

16.

Zhang F, Cui J, Liu X, Lv B, Liu X, Xie Z . Roles of microRNA-34a targeting SIRT1 in mesenchymal stem cells. Stem Cell Res Ther. 2015; 6:195. PMC: 4597437. DOI: 10.1186/s13287-015-0187-x. View

17.

Zeng B, Liu L, Liao X, Zhang C, Ruan H . Thyroid hormone protects cardiomyocytes from HO-induced oxidative stress via the PI3K-AKT signaling pathway. Exp Cell Res. 2019; 380(2):205-215. DOI: 10.1016/j.yexcr.2019.05.003. View

18.

Lv P, Zhou M, He J, Meng W, Ma X, Dong S . Circulating miR-208b and miR-34a are associated with left ventricular remodeling after acute myocardial infarction. Int J Mol Sci. 2014; 15(4):5774-88. PMC: 4013595. DOI: 10.3390/ijms15045774. View

19.

Zhou X, Wan L, Xu Q, Zhao Y, Liu J . Notch signaling activation contributes to cardioprotection provided by ischemic preconditioning and postconditioning. J Transl Med. 2013; 11:251. PMC: 3853230. DOI: 10.1186/1479-5876-11-251. View

20.

Feng Y, Huang W, Meng W, Jegga A, Wang Y, Cai W . Heat shock improves Sca-1+ stem cell survival and directs ischemic cardiomyocytes toward a prosurvival phenotype via exosomal transfer: a critical role for HSF1/miR-34a/HSP70 pathway. Stem Cells. 2013; 32(2):462-72. PMC: 5517317. DOI: 10.1002/stem.1571. View