{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:03:36Z","timestamp":1785197016010,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Marfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene, leading to alterations in the extracellular matrix microfibril assembly and the early formation of thoracic aorta aneurysms (TAAs). Non-genetic TAAs share many clinico-pathological aspects with MFS and deregulation of some microRNAs (miRNAs) has been demonstrated to be involved in the progression of TAA. In this study, 40 patients undergoing elective ascending aorta surgery were enrolled to compare TAA histomorphological features, miRNA profile and related target genes in order to find specific alterations that may explain the earlier and more severe clinical outcomes in MFS patients. Histomorphological, ultrastructural and in vitro studies were performed in order to compare aortic wall features of MFS and non-MFS TAA. MFS displayed greater glycosaminoglycan accumulation and loss\/fragmentation of elastic fibers compared to non-MFS TAA. Immunohistochemistry revealed increased CD133+ angiogenic remodeling, greater MMP-2 expression, inflammation and smooth muscle cell (SMC) turnover in MFS TAA. Cultured SMCs from MFS confirmed higher turnover and \u03b1-smooth muscle actin expression compared with non-MFS TAA. Moreover, twenty-five miRNAs, including miR-26a, miR-29, miR-143 and miR-145, were found to be downregulated and only miR-632 was upregulated in MFS TAA in vivo. Bioinformatics analysis revealed that some deregulated miRNAs in MFS TAA are implicated in cell proliferation, extracellular matrix structure\/function and TGF\u03b2 signaling. Finally, gene analysis showed 28 upregulated and seven downregulated genes in MFS TAA, some of them belonging to the CDH1\/APC and CCNA2\/TP53 signaling pathways. Specific miRNA and gene deregulation characterized the aortopathy of MFS and this was associated with increased angiogenic remodeling, likely favoring the early and more severe clinical outcomes, compared to non-MFS TAA. Our findings provide new insights concerning the pathogenetic mechanisms of MFS TAA; further investigation is needed to confirm if these newly identified specific deregulated miRNAs may represent potential therapeutic targets to counteract the rapid progression of MFS aortopathy.<\/jats:p>","DOI":"10.3390\/ijms21186886","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T21:20:28Z","timestamp":1600636828000},"page":"6886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Specific miRNA and Gene Deregulation Characterize the Increased Angiogenic Remodeling of Thoracic Aneurysmatic Aortopathy in Marfan Syndrome"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-4922","authenticated-orcid":false,"given":"Federico","family":"D\u2019Amico","sequence":"first","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Doldo","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6488-1965","authenticated-orcid":false,"given":"Calogera","family":"Pisano","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Scioli","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Centofanti","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Proietti","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Falconi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6227-4248","authenticated-orcid":false,"given":"Federica","family":"Sangiuolo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedeo","family":"Ferlosio","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ruvolo","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-5854","authenticated-orcid":false,"given":"Augusto","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,19]]},"reference":[{"key":"ref_1","unstructured":"Salik, I., and Rawla, P. (2020). Marfan Syndrome, StatPearls."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1136\/jmg.2005.039669","article-title":"The molecular genetics of Marfan syndrome and related disorders","volume":"43","author":"Robinson","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.semcdb.2018.07.016","article-title":"Fibrillin microfibrils and elastic fiber proteins: Functional interactions and extracellular regulation of growth factors","volume":"89","author":"Thomson","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1161\/CIRCRESAHA.113.300675","article-title":"Genetics of thoracic aortic aneurysm: At the crossroad of transforming growth factor-beta signaling and vascular smooth muscle cell contractility","volume":"113","author":"Gillis","year":"2013","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e150","DOI":"10.1161\/01.CIR.0000155243.70456.F4","article-title":"Treatment of aortic disease in patients with Marfan syndrome","volume":"111","author":"Milewicz","year":"2005","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000151766","article-title":"Transforming growth factor-beta signaling in thoracic aortic aneurysm development: A paradox in pathogenesis","volume":"46","author":"Jones","year":"2009","journal-title":"J. Vasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Van Andel, M.M., Groenink, M., Zwinderman, A.H., Mulder, B.J.M., and de Waard, V. (2019). The Potential Beneficial Effects of Resveratrol on Cardiovascular Complications in Marfan Syndrome Patients Insights from Rodent-Based Animal Studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051122"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1136\/hrt.2010.212100","article-title":"The translational science of Marfan syndrome","volume":"97","author":"Jondeau","year":"2011","journal-title":"Heart"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/cvr\/cvw039","article-title":"The multifactorial nature of microRNAs in vascular remodeling","volume":"110","author":"Welten","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/hrt.2004.055111","article-title":"Aortic dimensions and the risk of dissection","volume":"92","author":"Erbel","year":"2006","journal-title":"Heart"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1161\/01.ATV.14.6.982","article-title":"Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro","volume":"14","author":"Orlandi","year":"1994","journal-title":"Arterioscler. Thromb."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1152\/physrev.00041.2008","article-title":"Vascular extracellular matrix and arterial mechanics","volume":"89","author":"Wagenseil","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0021-9150(91)90003-L","article-title":"Aging and atherosclerosis in the rabbit. 1. Distribution, prevalence and morphology of atherosclerotic lesions","volume":"89","author":"Spagnoli","year":"1991","journal-title":"Atherosclerosis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1161\/01.CIR.11.3.321","article-title":"The cardiovascular aspects of Marfan\u2019s syndrome: A heritable disorder of connective tissue","volume":"11","author":"McKusick","year":"1955","journal-title":"Circulation"},{"key":"ref_15","first-page":"717","article-title":"Medionecrosis Aortae Idiopathica Cystica","volume":"8","author":"Moritz","year":"1932","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.carpath.2014.04.007","article-title":"Aortopathy in Marfan syndrome: An update","volume":"23","author":"Romaniello","year":"2014","journal-title":"Cardiovasc. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1161\/CIRCULATIONAHA.107.693523","article-title":"Medical management of Marfan syndrome","volume":"117","author":"Keane","year":"2008","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1161\/01.ATV.20.4.1123","article-title":"Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits","volume":"20","author":"Orlandi","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13059-017-1243-x","article-title":"MicroRNAs control mRNA fate by compartmentalization based on 3\u2032 UTR length in male germ cells","volume":"18","author":"Zhang","year":"2017","journal-title":"Genome Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.jvs.2010.11.113","article-title":"A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis","volume":"53","author":"Liao","year":"2011","journal-title":"J. Vasc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"831641","DOI":"10.1155\/2015\/831641","article-title":"MicroRNAs: Novel Players in Aortic Aneurysm","volume":"2015","author":"Fu","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12967-018-1429-3","article-title":"Deregulated microRNA and mRNA expression profiles in the peripheral blood of patients with Marfan syndrome","volume":"16","author":"Kahraman","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/cvr\/cvy022","article-title":"Smooth muscle cell fate and plasticity in atherosclerosis","volume":"114","author":"Allahverdian","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/cvr\/cvu196","article-title":"Angiogenesis and remodelling in human thoracic aortic aneurysms","volume":"104","author":"Kessler","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/01.RES.88.1.37","article-title":"Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome","volume":"88","author":"Bunton","year":"2001","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1161\/ATVBAHA.114.304412","article-title":"Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome","volume":"35","author":"Meirelles","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1161\/ATVBAHA.120.314670","article-title":"Single-Cell Transcriptomic Profiling of Vascular Smooth Muscle Cell Phenotype Modulation in Marfan Syndrome Aortic Aneurysm","volume":"40","author":"Pedroza","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dale, M., Fitzgerald, M.P., Liu, Z., Meisinger, T., Karpisek, A., Purcell, L.N., Carson, J.S., Harding, P., Lang, H., and Koutakis, P. (2017). Premature aortic smooth muscle cell differentiation contributes to matrix dysregulation in Marfan Syndrome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186603"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1006\/excr.1994.1290","article-title":"Proliferative activity and alpha-smooth muscle actin expression in cultured rat aortic smooth muscle cells are differently modulated by transforming growth factor-beta 1 and heparin","volume":"214","author":"Orlandi","year":"1994","journal-title":"Exp. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1161\/01.ATV.0000142805.20398.74","article-title":"Hemodynamic regulation of CD34+ cell localization and differentiation in experimental aneurysms","volume":"24","author":"Sho","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1196\/annals.1383.011","article-title":"Endothelial progenitor cells and abdominal aortic aneurysms","volume":"1085","author":"Dawson","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.3892\/ijmm.2012.1108","article-title":"Contribution of endothelial progenitor cells to neovascularization (Review)","volume":"30","author":"Li","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3389\/fonc.2019.00308","article-title":"Endothelial Cell-Derived TGF-beta Promotes Epithelial-Mesenchymal Transition via CD133 in HBx-Infected Hepatoma Cells","volume":"9","author":"Rawal","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cafueri, G., Parodi, F., Pistorio, A., Bertolotto, M., Ventura, F., Gambini, C., Bianco, P., Dallegri, F., Pistoia, V., and Pezzolo, A. (2012). Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035312"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.surg.2004.12.003","article-title":"Relationship between iNOS expression and aortic cell proliferation and apoptosis in an elastase-induced model of aorta aneurysm and the effect of 1400 W administration","volume":"137","author":"Sigala","year":"2005","journal-title":"Surgery"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jtcvs.2005.09.018","article-title":"Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections","volume":"131","author":"He","year":"2006","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Radonic, T., de Witte, P., Groenink, M., de Waard, V., Lutter, R., van Eijk, M., Jansen, M., Timmermans, J., Kempers, M., and Scholte, A.J. (2012). Inflammation aggravates disease severity in Marfan syndrome patients. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032963"},{"key":"ref_38","first-page":"289","article-title":"Neovascularization with chronic inflammation characterizes ascending aortic dissection","volume":"20","author":"Niinimak","year":"2018","journal-title":"Anatol. J. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1161\/01.ATV.0000199393.74656.4c","article-title":"Phenotypic modulation of intima and media smooth muscle cells in fatal cases of coronary artery lesion","volume":"26","author":"Hao","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Takeda, N., Hara, H., Fujiwara, T., Kanaya, T., Maemura, S., and Komuro, I. (2018). TGF-beta Signaling-Related Genes and Thoracic Aortic Aneurysms and Dissections. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072125"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/jcp.22422","article-title":"MicroRNA-26a is a novel regulator of vascular smooth muscle cell function","volume":"226","author":"Leeper","year":"2011","journal-title":"J. Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1038\/s41467-017-01737-4","article-title":"Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling","volume":"8","author":"Sassi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1161\/ATVBAHA.116.307841","article-title":"Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G\/+ Marfan Mouse Model","volume":"36","author":"Hibender","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e13257","DOI":"10.14814\/phy2.13257","article-title":"Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model","volume":"5","author":"Okamura","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1161\/CIRCRESAHA.111.253740","article-title":"miR-29b participates in early aneurysm development in Marfan syndrome","volume":"110","author":"Merk","year":"2012","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1038\/cdd.2009.153","article-title":"The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: Correlates with human disease","volume":"16","author":"Elia","year":"2009","journal-title":"Cell Death. Differ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1161\/CIRCRESAHA.112.277368","article-title":"Modulation of smooth muscle cell phenotype: The other side of the story","volume":"111","author":"Huang","year":"2012","journal-title":"Circ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1159\/000460510","article-title":"MicroRNA-29b Inhibits Angiogenesis by Targeting VEGFA through the MAPK\/ERK and PI3K\/Akt Signaling Pathways in Endometrial Carcinoma","volume":"41","author":"Chen","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1002\/hep.26941","article-title":"MicroRNA-26a suppresses angiogenesis in human hepatocellular carcinoma by targeting hepatocyte growth factor-cMet pathway","volume":"59","author":"Yang","year":"2014","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11010-018-3313-0","article-title":"MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma","volume":"448","author":"Liu","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37458","DOI":"10.18632\/oncotarget.6059","article-title":"MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers","volume":"6","author":"Liu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/labinvest.2012.87","article-title":"Micro-RNA-632 downregulates DNAJB6 in breast cancer","volume":"92","author":"Mitra","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2162-3619-2-17","article-title":"CD133: A stem cell biomarker and beyond","volume":"2","author":"Li","year":"2013","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1006\/excr.2001.5294","article-title":"Upregulation of the cochaperone Mdg1 in endothelial cells is induced by stress and during in vitro angiogenesis","volume":"269","author":"Prols","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1210\/endo.143.4.8731","article-title":"The angiogenic factor cysteine-rich 61 (CYR61, CCN1) supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans","volume":"143","author":"Grzeszkiewicz","year":"2002","journal-title":"Endocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0014-2999(03)02040-5","article-title":"Iloprost down-regulates the expression of the growth regulatory gene Cyr61 in human vascular smooth muscle cells","volume":"474","author":"Debey","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/path.1400","article-title":"Extracellular matrix remodeling: The role of matrix metalloproteinases","volume":"200","author":"Stamenkovic","year":"2003","journal-title":"J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.celrep.2015.09.049","article-title":"Matrix Remodeling Promotes Pulmonary Hypertension through Feedback Mechanoactivation of the YAP\/TAZ-miR-130\/301 Circuit","volume":"13","author":"Bertero","year":"2015","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/jcp.1068","article-title":"Requirement of protein kinase Calpha, extracellular matrix remodeling, and cell-matrix interaction for transforming growth factorbeta-regulated expression of E-cadherin and catenins","volume":"187","author":"Wang","year":"2001","journal-title":"J. Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.molcel.2013.04.029","article-title":"Coordinate transcriptional and translational repression of p53 by TGF-beta1 impairs the stress response","volume":"50","author":"Gascard","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng1116","article-title":"Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome","volume":"33","author":"Neptune","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The revised Ghent nosology for the Marfan syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/ejechocard\/jeq056","article-title":"Echocardiography in aortic diseases: EAE recommendations for clinical practice","volume":"11","author":"Evangelista","year":"2010","journal-title":"Eur. J. Echocardiogr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/00000658-199109000-00013","article-title":"Sixteen-year experience with aortic root replacement. Results of 172 operations","volume":"214","author":"Kouchoukos","year":"1991","journal-title":"Ann. Surg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.yexcr.2005.10.008","article-title":"Phenotypic heterogeneity influences the behavior of rat aortic smooth muscle cells in collagen lattice","volume":"311","author":"Orlandi","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1161\/hq0701.092144","article-title":"Phenotypic heterogeneity influences apoptotic susceptibility to retinoic acid and cis-platinum of rat arterial smooth muscle cells in vitro: Implications for the evolution of experimental intimal thickening","volume":"21","author":"Orlandi","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/S0002-9440(10)62472-8","article-title":"Increased expression and activity of matrix metalloproteinases characterize embolic cardiac myxomas","volume":"166","author":"Orlandi","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0021-9150(01)00568-8","article-title":"Propionyl-L-carnitine reduces intimal hyperplasia after injury in normocholesterolemic rabbit carotid artery by modulating proliferation and caspase 3-dependent apoptosis of vascular smooth muscle cells","volume":"160","author":"Orlandi","year":"2002","journal-title":"Atherosclerosis"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.cardiores.2004.07.024","article-title":"Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit","volume":"64","author":"Orlandi","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-4939-6563-2_2","article-title":"Functional Analysis of miRNAs Using the DIANA Tools Online Suite","volume":"1517","author":"Vlachos","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kulkarni, M.M. (2011). Digital multiplexed gene expression analysis using the NanoString nCounter system. Curr. Protoc. Mol. Biol.","DOI":"10.1002\/0471142727.mb25b10s94"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:11:42Z","timestamp":1760177502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,19]]},"references-count":71,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21186886"],"URL":"https:\/\/doi.org\/10.3390\/ijms21186886","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,19]]}}}