Aortic dissection (AD) caused by the tear in the aortic wall threatens aorta, causing severe chest pain, syncope and even death. Fortunately, development of genetic technology provides promising approaches for AD treatment. To analyze impacts of miR-15a-5p on modulating cell viability and migratory ability of vascular smooth muscle cells (VSMCs). Ang II (0, 0.05 and 0.1 microM) treatment were applied for inducing inflammatory reactions of VSMCs. RNA expressions of miR-15a-5p with Bcl-2 was examined using RT-qPCR. CCK-8 and transwell evaluated cell viability and migratory ability, respectively. The binding about miR-15a-5p with Bcl-2 were detected by luciferase reporter assay. Western blot detected protein expressions of Bcl-2, MCP-1 and MMP-9. Ang II treatment not only accelerated VSMCs viability and migratory abilities, but also upregulated MCP-1 and MMP-9 protein expressions. MiR-15a-5p was detected to be promoted by Ang II. However, miR-15a-5p inhibitor decreased VSMC cell viability and migratory ability and suppressed protein expressions of MCP-1 and MMP-9. Bcl-2 was targeted and downregulated by miR-15a-5p. Nevertheless, high VSMC cell viability and migration caused by miR-15a-5p overexpression were hindered with overexpressed Bcl-2. MiR-15a-5p mimics also elevated MCP-1 and MMP-9 protein expressions, which were inhibited by Bcl-2 upregulation.

Department of Cardiac Surgery Xingtai People's Hospital Xingtai City Hebei Province China

See more in PubMed

Tchana-Sato V, Sakalihasan N, Defraigne JO. Aortic dissection. (Article in French) Rev Med Liege. 2018;73:290–295. PubMed

Zhu Y, Lingala B, Baiocchi B, Tao JJ, Arana VT, Khoo JW, Williams KM, et al. Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective. J Am Coll Cardiol. 2020;76:1703–1713. doi: 10.1016/j.jacc.2020.07.061. PubMed DOI

Nienaber CA, Clough RE, Sakalihasan N, Suzuki T, Gibbs R, Mussa F, Jenkins MP, et al. Aortic dissection. Nat Rev Dis Primers. 2016;2:16053. doi: 10.1038/nrdp.2016.53. PubMed DOI

Gawinecka J, Schönrath F, von Eckardstein A. Acute aortic dissection: pathogenesis, risk factors and diagnosis. Swiss Med Wkly. 2017;147:w14489. doi: 10.4414/smw.2017.14489. PubMed DOI

Dong N, Piao H, Li B, Xu J, Wei S, Liu K. Poor management of hypertension is an important precipitating factor for the development of acute aortic dissection. J Clin Hypertens (Greenwich) 2019;21:804–812. doi: 10.1111/jch.13556. PubMed DOI PMC

Wu D, Shen YH, Russell L, Coselli JS, LeMaire SA. Molecular mechanisms of thoracic aortic dissection. J Surg Res. 2013;184:907–924. doi: 10.1016/j.jss.2013.06.007. PubMed DOI PMC

Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, Evangelista A, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA. 2000;283:897–903. doi: 10.1001/jama.283.7.897. PubMed DOI

Akutsu K. Etiology of aortic dissection. Gen Thorac Cardiovasc Surg. 2019;67:271–276. doi: 10.1007/s11748-019-01066-x. PubMed DOI

Shi Y, Liu B, Wang C-S, Yang C-S. MST1 down-regulation in decreasing apoptosis of aortic dissection smooth muscle cell apoptosis. Eur Rev Med Pharmacol Sci. 2018;22:2044–2051. doi: 10.26355/eurrev_201804_14734. PubMed DOI

Riches K, Clark E, Helliwell RJ, Angelini TG, Hemmings KE, Bailey MA, Bridge I, Scott DJA, Porter KE. Progressive development of aberrant smooth muscle cell phenotype in abdominal aortic aneurysm disease. J Vasc Res. 2018;55:35–46. doi: 10.1159/000484088. PubMed DOI

Cheng M, Yang Y, Xin H, Li M, Zong T, He T, Yu T, Xin H. Non-coding RNAs in aortic dissection: From biomarkers to therapeutic targets. J Cell Mol Med. 2020;24:11622–11637. doi: 10.1111/jcmm.15802. PubMed DOI PMC

Sbarouni E, Georgiadou P. MicroRNAs in acute aortic dissection. J Thorac Dis. 2018;10:1256–1257. doi: 10.21037/jtd.2018.03.27. PubMed DOI PMC

Barwari T, Joshi A, Mayr M. MicroRNAs in cardiovascular disease. J Am Coll Cardiol. 2016;68:2577–2584. doi: 10.1016/j.jacc.2016.09.945. PubMed DOI

Su Y, Li Q, Zheng Z, Wei X, Hou P. Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in aortic dissection. Medicine (Baltimore) 2019;98:e16013. doi: 10.1097/MD.0000000000016013. PubMed DOI PMC

Zhang W, Li Y, Xi X, Zhu G, Wang S, Liu S, Song M. MicroRNA-15a-5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP-2 signaling pathway. Int J Mol Med. 2020;45:461–474. doi: 10.3892/ijmm.2019.4434. PubMed DOI PMC

Gao P, Si J, Yang B, Yu J. Upregulation of MicroRNA-15a contributes to pathogenesis of Abdominal Aortic Aneurysm (AAA) by modulating the expression of Cyclin-dependent kinase inhibitor 2B (CDKN2B) Med Sci Monit. 2017;23:881–888. doi: 10.12659/MSM.898233. PubMed DOI PMC

Dong J, Bao J, Feng R, Zhao Z, Lu Q, Wang G, Li H, et al. Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection. Sci Rep. 2017;7:12784. doi: 10.1038/s41598-017-13104-w. PubMed DOI PMC

Ebrahim AS, Sabbagh H, Liddane A, Raufi A, Kandouz M, Al-Katib A. Hematologic malignancies: newer strategies to counter the BCL-2 protein. J Cancer Res Clin Oncol. 2016;142:2013–2022. doi: 10.1007/s00432-016-2144-1. PubMed DOI PMC

Perlman H, Sata M, Krasinski K, Dorai T, Buttyan R, Walsh K. Adenovirus-encoded hammerhead ribozyme to Bcl-2 inhibits neointimal hyperplasia and induces vascular smooth muscle cell apoptosis. Cardiovasc Res. 2000;45:570–578. doi: 10.1016/S0008-6363(99)00346-6. PubMed DOI

Teng H, Li M, Qian L, Yang H, Pang M. Long non-coding RNA SNHG16 inhibits the oxygen-glucose deprivation and reoxygenation-induced apoptosis in human brain microvascular endothelial cells by regulating miR-15a-5p/bcl-2. Mol Med Rep. 2020;22:2685–2694. doi: 10.3892/mmr.2020.11385. PubMed DOI PMC

Singh S, Anshita D, Ravichandiran V. MCP-1: Function, regulation, and involvement in disease. Int Immunopharmacol. 2021;101:107598. doi: 10.1016/j.intimp.2021.107598. PubMed DOI PMC

Choi JM, Baek SE, Kim JO, Jeon EY, Jang EJ, Kim CD. 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis. Sci Rep. 2021;11:11100. doi: 10.1038/s41598-021-90636-2. PubMed DOI PMC

Ito S, Hashimoto Y, Majima R, Nakao E, Aoki H, Nishihara M, Ohno-Urabe S, et al. MRTF-A promotes angiotensin II-induced inflammatory response and aortic dissection in mice. PLoS One. 2020;15:e0229888. doi: 10.1371/journal.pone.0229888. PubMed DOI PMC

Shih Y-C, Chen P-Y, Ko T-M, Huang P-H, Ma H, Tarng D-C. MMP-9 deletion attenuates arteriovenous fistula neointima through reduced perioperative vascular inflammation. Int J Mol Sci. 2021;22:5448. doi: 10.3390/ijms22115448. PubMed DOI PMC

Li X, Liu D, Zhao L, Wang L, Li Y, Cho K, Tao C, Jiang B. Targeted depletion of monocyte/macrophage suppresses aortic dissection with the spatial regulation of MMP-9 in the aorta. Life Sci. 2020;254:116927. doi: 10.1016/j.lfs.2019.116927. PubMed DOI

Yamaki F, Obara K, Tanaka Y. Angiotensin II regulates excitability and contractile functions of myocardium and smooth muscles through autonomic nervous transmission. (Article in Japanese) Yakugaku Zasshi. 2019;139:793–805. doi: 10.1248/yakushi.19-00002. PubMed DOI

Huo YB, Gao X, Peng Q, Nie Q, Bi W. Dihydroartemisinin alleviates AngII-induced vascular smooth muscle cell proliferation and inflammatory response by blocking the FTO/NR4A3 axis. Inflamm Res. 2022;71:243–253. doi: 10.1007/s00011-021-01533-3. PubMed DOI

Wu Z, Dai F, Ren W, Liu H, Li B, Chang J. Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1. Am J Transl Res. 2016;8:28–36. PubMed PMC

Vavuranakis M, Kariori M, Vrachatis D, Aznaouridis K, Siasos G, Kokkou E, Mazariset S, et al. MicroRNAs in aortic disease. Curr Top Med Chem. 2013;13:1559–1572. doi: 10.2174/15680266113139990105. PubMed DOI

Xu Z, Wang Q, Pan J, Sheng X, Hou D, Chong H, Wei Z, Zheng S, et al. Characterization of serum miRNAs as molecular biomarkers for acute Stanford type A aortic dissection diagnosis. Sci Rep. 2017;7:13659. doi: 10.1038/s41598-017-13696-3. PubMed DOI PMC

Qiu ZH, He J, Chai TC, Zhang Y-L, Zhou H, Zheng H, Chen X-S, Zhang L, Li Y-M, Chen L-W. miR-145 attenuates phenotypic transformation of aortic vascular smooth muscle cells to prevent aortic dissection. J Clin Lab Anal. 2021;35:e23773. doi: 10.1002/jcla.23773. PubMed DOI PMC

Zheng X, Li A, Zhao L, Zhou T, Shen Q, Cui Q, Qin Q. Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells. Biochem Biophys Res Commun. 2013;437:625–631. doi: 10.1016/j.bbrc.2013.07.017. PubMed DOI

Wei C, Li L, Gupta S. NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2. Mol Cell Biochem. 2014;387:135–141. doi: 10.1007/s11010-013-1878-1. PubMed DOI

Rybka V, Suzuki YJ, Shults NV. Effects of Bcl-2/Bcl-xL inhibitors on pulmonary artery smooth muscle cells. Antioxidants (Basel) 2018;7:150. doi: 10.3390/antiox7110150. PubMed DOI PMC

Leng J, Song Q, Zhao Y, Wang Z. miR-15a represses cancer cell migration and invasion under conditions of hypoxia by targeting and downregulating Bcl-2 expression in human osteosarcoma cells. Int J Oncol. 2018;52:1095–1104. doi: 10.3892/ijo.2018.4285. PubMed DOI PMC

Fluid shear stress-induced down-regulation of miR-146a-5p inhibits osteoblast apoptosis via targeting SMAD4