MicroRNA Profiling in Dogs Undergoing Induced Ischemic Heart Infarction: An Experimental Study

Overview

Journal Vet World

Specialty Veterinary Medicine

Date 2023 Aug 14

PMID 37577186

Authors

Liqaa A Raffee

Khaled Z Alawneh

Musa Ahmed Mohammed Alshehabat

Hazem Haddad

Saied A Jaradat

Affiliations

Soon will be listed here.

Abstract

Background And Aim: MicroRNAs (miRNAs) play an important role in various biological functions. According to many studies, miRNA expression is tissue-specific, strongly controlled throughout embryogenesis, and over- or under-expressed in numerous disorders, including cardiovascular pathologies. This study aimed to screen, characterize, and profile many induced biomarkers (miRNAs) in dog serum before and after experimentally inducing a regional myocardial infarction (MI) by occluding the coronary arteries under general anesthesia.

Materials And Methods: A preclinical experimental animal study recruited 12 healthy canine dogs. The selected canine dogs were anesthetized with 1 mg/kg xylazine and 15 mg/kg ketamine before undergoing femoral arterial catheterization under fluoroscopic supervision. Commercial assay kits were used to purify total RNA and miRNA before the occlusion and 2 h after the occlusion according to the manufacturer's guidelines, and the samples were stored in RNase/DNase-free water at -80°C. Data were analyzed by GraphPad Prism 5.0 software (GraphPad Prism, San Diego, CA) SPSS, and GenEx software (www.multid.se) or (REST V3).

Results: Among 325 transcribed genes, 20 were identified in 2 h. After MI, 14 biomarkers were negative, indicating downregulation, and 6 (3-F08, 3-B10, 4-A11, 1-A06, 2-E01, 3-F10) were positive, indicating upregulation. Polymerase chain reaction assay results showed a normalized fold-change in gene expression in the test sample. Fold values >1 represented a biologically significant change.

Conclusion: Profiling of miRNAs before and after MI in a dog model revealed upregulation of six previously unidentified biomarkers (3-F08, 3-B10, 4-A11, 1-A06, 2-E01, and 3-F10), indicating various miRNA regulatory patterns.

References

Alawneh K, Raffee L, Alshehabat M, Haddad H, Jaradat S . Characterizing and Profiling microRNAs in Dogs Undergoing Induced Ischemic Brain Stroke After Middle Cerebral Artery Occlusion Under Fluoroscopic Guidance. Vasc Health Risk Manag. 2021; 17:543-550. PMC: 8435620. DOI: 10.2147/VHRM.S317861. View

Nam D, Ni C, Rezvan A, Suo J, Budzyn K, Llanos A . Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis. Am J Physiol Heart Circ Physiol. 2009; 297(4):H1535-43. PMC: 2770764. DOI: 10.1152/ajpheart.00510.2009. View

Malakar A, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S . A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019; 234(10):16812-16823. DOI: 10.1002/jcp.28350. View

Tang Q, Lei H, Wu H, Chen J, Deng C, Sheng W . Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy. Acta Pharmacol Sin. 2018; 40(2):208-215. PMC: 6329771. DOI: 10.1038/s41401-018-0041-7. View

Wang K, Zhao X, Liu Y, Zeng Q, Mao X, Li S . Circulating MiR-19b-3p, MiR-134-5p and MiR-186-5p are Promising Novel Biomarkers for Early Diagnosis of Acute Myocardial Infarction. Cell Physiol Biochem. 2016; 38(3):1015-29. DOI: 10.1159/000443053. View

Cakmak H, Coskunpinar E, Ikitimur B, Barman H, Karadag B, Tiryakioglu N . The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med (Hagerstown). 2015; 16(6):431-7. DOI: 10.2459/JCM.0000000000000233. View

Izarra A, Moscoso I, Levent E, Canon S, Cerrada I, Diez-Juan A . miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction. Stem Cell Reports. 2014; 3(6):1029-42. PMC: 4264058. DOI: 10.1016/j.stemcr.2014.10.010. View

Velle-Forbord T, Eidlaug M, Debik J, Saether J, Follestad T, Nauman J . Circulating microRNAs as predictive biomarkers of myocardial infarction: Evidence from the HUNT study. Atherosclerosis. 2019; 289:1-7. DOI: 10.1016/j.atherosclerosis.2019.07.024. View

Bray F, Laversanne M, Weiderpass E, Soerjomataram I . The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer. 2021; 127(16):3029-3030. DOI: 10.1002/cncr.33587. View

10.

Yang M, Kong D, Chen J . Inhibition of miR-148b ameliorates myocardial ischemia/reperfusion injury via regulation of Wnt/β-catenin signaling pathway. J Cell Physiol. 2019; 234(10):17757-17766. DOI: 10.1002/jcp.28401. View

11.

Tao H, Dai C, Ding J, Yang J, Ding X, Xu S . Epigenetic aberrations of miR-369-5p and DNMT3A control Patched1 signal pathway in cardiac fibrosis. Toxicology. 2018; 410:182-192. DOI: 10.1016/j.tox.2018.08.004. View

12.

Bicciato G, Arnold M, Gebhardt A, Katan M . Precision medicine in secondary prevention of ischemic stroke: how may blood-based biomarkers help in clinical routine? An expert opinion. Curr Opin Neurol. 2021; 35(1):45-54. DOI: 10.1097/WCO.0000000000001011. View

13.

Wang L, Liu J, Xu B, Liu Y, Liu Z . Reduced exosome miR-425 and miR-744 in the plasma represents the progression of fibrosis and heart failure. Kaohsiung J Med Sci. 2018; 34(11):626-633. DOI: 10.1016/j.kjms.2018.05.008. View

14.

Specjalski K, Jassem E . MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?. Arch Immunol Ther Exp (Warsz). 2019; 67(4):213-223. PMC: 6597590. DOI: 10.1007/s00005-019-00547-4. View

15.

Siasos G, Bletsa E, Stampouloglou P, Oikonomou E, Tsigkou V, Paschou S . MicroRNAs in cardiovascular disease. Hellenic J Cardiol. 2020; 61(3):165-173. DOI: 10.1016/j.hjc.2020.03.003. View

16.

Gong J, Yang Y, Wang J, Li Y, Guo X, Huang Q . Expression of miR-93-5p as a Potential Predictor of the Severity of Chronic Thromboembolic Pulmonary Hypertension. Biomed Res Int. 2021; 2021:6634417. PMC: 8075669. DOI: 10.1155/2021/6634417. View

17.

Lou S, Sun T, Li H, Hu Z . Mechanisms of microRNA-mediated gene regulation in unicellular model alga . Biotechnol Biofuels. 2018; 11:244. PMC: 6129010. DOI: 10.1186/s13068-018-1249-y. View

18.

Kiyohara K, Sakai T, Nishiyama C, Nishiuchi T, Hayashi Y, Iwami T . Epidemiology of Out-of-Hospital Cardiac Arrest Due to Suffocation Focusing on Suffocation Due to Japanese Rice Cake: A Population-Based Observational Study From the Utstein Osaka Project. J Epidemiol. 2017; 28(2):67-74. PMC: 5792229. DOI: 10.2188/jea.JE20160179. View

19.

Li H, Hastings M, Rhee J, Trager L, Roh J, Rosenzweig A . Targeting Age-Related Pathways in Heart Failure. Circ Res. 2020; 126(4):533-551. PMC: 7041880. DOI: 10.1161/CIRCRESAHA.119.315889. View

20.

Kumar S, Williams D, Sur S, Wang J, Jo H . Role of flow-sensitive microRNAs and long noncoding RNAs in vascular dysfunction and atherosclerosis. Vascul Pharmacol. 2018; 114:76-92. PMC: 6905428. DOI: 10.1016/j.vph.2018.10.001. View