Two MicroRNAs, miR-34a and miR-125a, Are Implicated in Bicuspid Aortopathy by Modulating Metalloproteinase 2
Tóm tắt
It has been recognized that wall shear stress plays an important role in the development of Bicuspid Aortopathy (BA), but the intrinsic mechanism is not well elucidated. This study aims to explore the underlying relationship between hemodynamical forces and pathological phenomenon. Total RNA was prepared from aortic wall tissues collected from 20 BA patients. RNA sequencing, bioinformatic analysis and quantitative reverse-transcription PCR validation identified nine miRNAs that were up-regulated in the aortic part exposed to high wall shear stress compared to the low wall shear stress control, and six miRNAs that were down-regulated. Among these candidates, miR-34a and miR-125a, both down-regulated in the high wall shear stress parts, were shown to be potential inhibitors of the metalloproteinase 2 gene. Luciferase reporter assays confirmed that both miRNAs could inhibit the expression of metalloproteinase 2 mRNA in CRL1999 by complementing with its 3′ untranslated region. Conversely, immunofluorescence assays showed that inhibition of miR-34a or miR-125a could lead to increased metalloproteinase 2 protein level. On the other hand, both miR-34a and miR-125a were shown to alleviate stretch-induced stimulation of metalloproteinase 2 expression in CRL1999 cells. The results suggested that miR-34a and miR-125a might be implicated in wall shear stress induced aortic pathogenesis due to their apparent regulatory roles in metalloproteinase 2 expression and extracellular matrix remodeling, which are key events in the weakening of aortic walls among BA patients.
Tài liệu tham khảo
Abdulkareem N, Smelt J, Jahangiri M (2013) Bicuspid aortic valve aortopathy: genetics, pathophysiology and medical therapy. Interact Cardiovasc Thorac Surg 17:554–559
Adamo L, Braverman AC (2015) Surgical threshold for bicuspid aortic valve aneurysm: a case for individual decision-making. Heart 101:1361–1367
Bazan HA, Hatfield SA, O’Malley CB, Brooks AJ, Lightell D Jr, Woods TC (2015) Acute loss of miR-221 and miR-222 in the atherosclerotic plaque shoulder accompanies plaque rupture. Stroke 46:3285–3287
Bonachea EM, Chang SW, Zender G, LaHaye S, Fitzgerald-Butt S, McBride KL, Garg V (2014) Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve. Pediatr Res 76:211–216
Browatzki M, Larsen D, Pfeiffer CA, Gehrke SG, Schmidt J, Kranzhofer A, Katus HA, Kranzhofer R (2005) Angiotensin II stimulates matrix metalloproteinase secretion in human vascular smooth muscle cells via nuclear factor-kappaB and activator protein 1 in a redox-sensitive manner. J Vasc Res 42:415–423
Cai Y, Yu X, Hu S, Yu J (2009) A brief review on the mechanisms of miRNA regulation. Genom Proteom Bioinform 7:147–154
Cao K, Sucosky P (2016) Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets. Int J Numer Method Biomed Eng. https://doi.org/10.1002/cnm.2798
Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, Nigam V (2014) The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PloS one 9:e96577
Chen Y, Gorski DH (2008) Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111:1217–1226
Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW (2004) Bicuspid aortic valve is heritable. J Am Coll Cardiol 44:138–143
Didangelos A, Yin X, Mandal K, Baumert M, Jahangiri M, Mayr M (2010) Proteomics characterization of extracellular space components in the human aorta. Molecular & Cellular Proteomics : MCP 9:2048–2062
Doench JG, Sharp PA (2004) Specificity of microRNA target selection in translational repression. Genes Dev 18:504–511
Dzau VJ (2001) Theodore cooper lecture: tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis. Hypertension 37:1047–1052
Fedak PW, de Sa MP, Verma S, Nili N, Kazemian P, Butany J, Strauss BH, Weisel RD, David TE (2003) Vascular matrix remodeling in patients with bicuspid aortic valve malformations: implications for aortic dilatation. J Thorac Cardiovasc Surg 126:797–806
Foffa I, Ait Ali L, Panesi P, Mariani M, Festa P, Botto N, Vecoli C, Andreassi MG (2013) Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes in familial cases of bicuspid aortic valve. BMC Med Genet 14:44
Forte A, Della Corte A, Grossi M, Bancone C, Provenzano R, Finicelli M, De Feo M, De Santo LS, Nappi G, Cotrufo M et al (2013) Early cell changes and TGFbeta pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis. Clin Sci 124:97–108
Forte A, Bancone C, Cobellis G, Buonocore M, Santarpino G, Fischlein TJM, Cipollaro M, De Feo M, Della Corte A (2017) A possible early biomarker for bicuspid aortopathy: circulating transforming growth factor beta-1 to soluble endoglin ratio. Circ Res 120:1800–1811
Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90:251–262
Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D (2005) Mutations in NOTCH1 cause aortic valve disease. Nature 437:270–274
Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15:509–524
Hoffman JI, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39:1890–1900
Jiang S, Zhang LF, Zhang HW, Hu S, Lu MH, Liang S, Li B, Li Y, Li D, Wang ED, Liu MF (2012) A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J 31:1985–1998
Kugo H, Zaima N, Tanaka H, Mouri Y, Yanagimoto K, Hayamizu K, Hashimoto K, Sasaki T, Sano M, Yata T et al (2016) Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm. Sci Rep 6:31268
Kutz WE, Wang LW, Bader HL, Majors AK, Iwata K, Traboulsi EI, Sakai LY, Keene DR, Apte SS (2011) ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in extracellular matrix of cultured fibroblasts. J Biol Chem 286:17156–17167
Laforest B, Andelfinger G, Nemer M (2011) Loss of Gata5 in mice leads to bicuspid aortic valve. J Clin Investig 121:2876–2887
Langdon WB (2015) Performance of genetic programming optimised Bowtie2 on genome comparison and analytic testing (GCAT) benchmarks. BioData Min 8:1
LeMaire SA, Wang X, Wilks JA, Carter SA, Wen S, Won T, Leonardelli D, Anand G, Conklin LD, Wang XL et al (2005) Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves. J Surg Res 123:40–48
Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, Qi M, Trask BJ, Kuo WL, Cochran J et al (1997) Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet 16:243–251
Loomes KM, Underkoffler LA, Morabito J, Gottlieb S, Piccoli DA, Spinner NB, Baldwin HS, Oakey RJ (1999) The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. Hum Mol Genet 8:2443–2449
Michelena HI, Desjardins VA, Avierinos JF, Russo A, Nkomo VT, Sundt TM, Pellikka PA, Tajik AJ, Enriquez-Sarano M (2008) Natural history of asymptomatic patients with normally functioning or minimally dysfunctional bicuspid aortic valve in the community. Circulation 117:2776–2784
Mohamed SA, Hanke T, Schlueter C, Bullerdiek J, Sievers HH (2005) Ubiquitin fusion degradation 1-like gene dysregulation in bicuspid aortic valve. J Thorac Cardiovasc Surg 130:1531–1536
Naito S, Petersen J, Sequeira-Gross T, Neumann N, Duque EJ, Zeller T, Reichenspurner H, Girdauskas E (2020) Bicuspid aortopathy—molecular involvement of microRNAs and MMP-TIMP. Biomarkers 25(8):711–718
Newby AC (2006) Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc Res 69:614–624
Nigam V, Sievers HH, Jensen BC, Sier HA, Simpson PC, Srivastava D, Mohamed SA (2010) Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves. J Heart Valve Dis 19:459–465
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JR, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P et al (2014) 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J AM COLL CARDIOL 63(22):e57–e185
Patel V, Carrion K, Hollands A, Hinton A, Gallegos T, Dyo J, Sasik R, Leire E, Hardiman G, Mohamed SA et al (2015) The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-kappaB signaling, and inflammatory gene expression in human aortic valve cells. FASEB J 29:1859–1868
Qiao P, Li G, Bi W, Yang L, Yao L, Wu D (2015) microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway. BMC Cancer 15:469
Quinlan AR (2014) BEDTools: the Swiss-army tool for genome feature analysis. Curr Protoc Bioinform. https://doi.org/10.1002/0471250953.bi1112s47
Rasheed Z, Al-Shobaili HA, Rasheed N, Mahmood A, Khan MI (2016) MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-kappaB pathway in human osteoarthritis chondrocytes. Arch Biochem Biophys 594:61–67
Roos-Hesselink JW, Scholzel BE, Heijdra RJ, Spitaels SE, Meijboom FJ, Boersma E, Bogers AJ, Simoons ML (2003) Aortic valve and aortic arch pathology after coarctation repair. Heart 89:1074–1077
Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, Gnyawali S, Shilo S, Nuovo GJ, Sen CK (2009) MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res 82:21–29
Shi LM, Tao JW, Qiu XB, Wang J, Yuan F, Xu L, Liu H, Li RG, Xu YJ, Wang Q et al (2014) GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve. Int J Mol Med 33:1219–1226
Szczesniak MW, Makalowska I (2014) miRNEST 2.0: a database of plant and animal microRNAs. Nucl Acids Res 42:74–77
Szeto K, Pastuszko P, del Alamo JC, Lasheras J, Nigam V (2013) Bicuspid aortic valves experience increased strain as compared to tricuspid aortic valves. World J Pediatr Congenit Heart Surg 4:362–366
Tischfield MA, Bosley TM, Salih MA, Alorainy IA, Sener EC, Nester MJ, Oystreck DT, Chan WM, Andrews C, Erickson RP, Engle EC (2005) Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nat Genet 37:1035–1037
van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 105:13027–13032
Wilton E, Bland M, Thompson M, Jahangiri M (2008) Matrix metalloproteinase expression in the ascending aorta and aortic valve. Interact Cardiovasc Thorac Surg 7:37–40
Wu J, Song HF, Li SH, Guo J, Tsang K, Tumiati L, Butany J, Yau TM, Ouzounian M, Fu S et al (2016) Progressive aortic dilation Is regulated by miR-17-associated miRNAs. J Am Coll Cardiol 67:2965–2977
Xue Y, Wei Z, Ding H, Wang Q, Zhou Z, Zheng S, Zhang Y, Hou D, Liu Y, Zen K et al (2015) MicroRNA-19b/221/222 induces endothelial cell dysfunction via suppression of PGC-1alpha in the progression of atherosclerosis. Atherosclerosis 241:671–681
Yap CH, Saikrishnan N, Tamilselvan G, Vasilyev N, Yoganathan AP (2012) The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface. Am J Physiol Heart Circ Physiol 303:H721-731
Zhang LF, Lou JT, Lu MH, Gao C, Zhao S, Li B, Liang S, Li Y, Li D, Liu MF (2015) Suppression of miR-199a maturation by HuR is crucial for hypoxia-induced glycolytic switch in hepatocellular carcinoma. EMBO J 34:2671–2685