{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:31:30Z","timestamp":1791426690422,"version":"4.3.3"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ascending thoracic aortic aneurysms arise from pathological tissue remodeling that leads to abnormal wall dilation and increases the risk of fatal dissection\/rupture. Large variability in disease manifestations across family members who carry a causative genetic variant for thoracic aortic aneurysms suggests that genetic modifiers may exacerbate clinical outcomes. Decreased perlecan expression in the aorta of mg\u0394<jats:sup><jats:italic>l<\/jats:italic><jats:italic>p<\/jats:italic><jats:italic>n<\/jats:italic><\/jats:sup> mice with severe Marfan syndrome phenotype advocates for exploring perlecan-encoding <jats:italic>Hspg2<\/jats:italic> as a candidate modifier gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To determine the effect of concurrent <jats:italic>Hspg2<\/jats:italic> and <jats:italic>Fbn1<\/jats:italic> mutations on the progression of thoracic aortopathy, we characterized the microstructure and passive mechanical response of the ascending thoracic aorta in female mice of four genetic backgrounds: wild-type, heterozygous with a mutation in the <jats:italic>Fbn1<\/jats:italic> gene (mg\u0394<jats:sup><jats:italic>l<\/jats:italic><jats:italic>p<\/jats:italic><jats:italic>n<\/jats:italic><\/jats:sup>), heterozygous with a mutation in the <jats:italic>Hspg2<\/jats:italic> gene (<jats:italic>Hspg2<\/jats:italic><jats:sup><jats:italic>+<\/jats:italic><jats:italic>\/<\/jats:italic><jats:italic>\u2212<\/jats:italic><\/jats:sup>), and double mutants carrying both the <jats:italic>Fbn1<\/jats:italic> and <jats:italic>Hspg2<\/jats:italic> variants (dMut).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elastic fiber fragmentation and medial disarray progress from the internal elastic lamina outward as the ascending thoracic aorta dilates in mg\u0394<jats:sup><jats:italic>l<\/jats:italic><jats:italic>p<\/jats:italic><jats:italic>n<\/jats:italic><\/jats:sup> and dMut mice. Concurrent increase in total collagen content relative to elastin reduces energy storage capacity and cyclic distensibility of aortic tissues from mice that carry the <jats:italic>Fbn1<\/jats:italic> variant. Inherent circumferential tissue stiffening strongly correlates with the severity of aortic dilatation in mg\u0394<jats:sup><jats:italic>l<\/jats:italic><jats:italic>p<\/jats:italic><jats:italic>n<\/jats:italic><\/jats:sup> and dMut mice. Perlecan haploinsufficiency superimposed to the mg\u0394<jats:sup><jats:italic>l<\/jats:italic><jats:italic>p<\/jats:italic><jats:italic>n<\/jats:italic><\/jats:sup> mutation curbs the viability of dMut mice, increases the occurrence of aortic enlargement, and reduces the axial stretch in aortic tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, our findings show that dMut mice are more vulnerable than mg\u0394<jats:sup><jats:italic>l<\/jats:italic><jats:italic>p<\/jats:italic><jats:italic>n<\/jats:italic><\/jats:sup> mice without an <jats:italic>Hspg2<\/jats:italic> mutation, yet later endpoints and additional structural and functional readouts are needed to identify causative mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2024.1319164","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T04:48:44Z","timestamp":1710305324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The Fbn1 gene variant governs passive ascending aortic mechanics in the mg\u0394lpn mouse model of Marfan syndrome when superimposed to perlecan haploinsufficiency"],"prefix":"10.3389","volume":"11","author":[{"given":"Samar A.","family":"Tarraf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Barbosa","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Herrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lygia V.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.jacc.2018.04.089","article-title":"Clinical validity of genes for heritable thoracic aortic aneurysm, dissection","volume":"72","author":"Renard","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3390\/biom10020182","article-title":"The genetics of thoracic aortic aneurysms, dissection: a clinical perspective","volume":"10","author":"Ostberg","year":"2020","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/jcp.21189","article-title":"Fibrillin-rich microfibrils: structural determinants of morphogenetic, homeostatic events","volume":"213","author":"Ramirez","year":"2007","journal-title":"J Cell Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cjca.2015.11.004","article-title":"Structure of the elastin-contractile units in the thoracic aorta, how genes that cause thoracic aortic aneurysms and dissections disrupt this structure","volume":"32","author":"Karimi","year":"2016","journal-title":"Can J Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s12265-012-9349-8","article-title":"Elastin in large artery stiffness and hypertension","volume":"5","author":"Wagenseil","year":"2012","journal-title":"J Cardiovasc Transl Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"H189","DOI":"10.1152\/ajpheart.00087.2018","article-title":"Elastin, arterial mechanics, and cardiovascular disease","volume":"315","author":"Cocciolone","year":"2018","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1161\/CIRCRESAHA.118.312436","article-title":"Genetics of thoracic and abdominal aortic diseases","volume":"124","author":"Pinard","year":"2019","journal-title":"Circ Res"},{"key":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1093\/eurheartj\/ehu281","article-title":"2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The task force for the diagnosis and treatment of Aortic Diseases of the European","volume":"35","author":"Erbel","year":"2014","journal-title":"Eur Heart J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1161\/CIRCULATIONAHA.107.702720","article-title":"Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD)","volume":"116","author":"Pape","year":"2007","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2022.10.021","article-title":"Aortic diameter is a poor predictor of aortic tissue failure metrics in patients with ascending aneurysms","author":"Vianna","year":"2022","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B12","doi-asserted-by":"publisher","first-page":"20161036","DOI":"10.1098\/rsif.2016.1036","article-title":"Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms","volume":"14","author":"Bellini","year":"2017","journal-title":"J R Soc Interface"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3819","DOI":"10.1073\/pnas.96.7.3819","article-title":"Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1","volume":"96","author":"Pereira","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"B14","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1172\/JCI20641","article-title":"Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome","volume":"114","author":"Judge","year":"2004","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1161\/CIRCRESAHA.109.207852","article-title":"Fibulin-4 deficiency results in ascending aortic aneurysms","volume":"106","author":"Huang","year":"2010","journal-title":"Circ Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e14136","DOI":"10.1371\/journal.pone.0014136","article-title":"A new mouse model for Marfan syndrome presents phenotypic variability associated with the genetic background and overall levels of Fbn1 expression","volume":"5","author":"Lima","year":"2010","journal-title":"PLoS ONE"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0224581","DOI":"10.1371\/journal.pone.0224581","article-title":"Association of thoracic spine deformity and cardiovascular disease in a mouse model for Marfan syndrome","volume":"14","author":"de Souza","year":"2019","journal-title":"PLoS ONE"},{"key":"B18","doi-asserted-by":"publisher","first-page":"108461","DOI":"10.1016\/j.exer.2021.108461","article-title":"The mg\u0394lpn mouse model for Marfan syndrome recapitulates the ocular phenotypes of the disease","volume":"204","author":"Souza","year":"2021","journal-title":"Exp Eye Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1161\/ATVBAHA.114.305150","article-title":"Dimorphic effects of transforming growth factor-\u03b2 signaling during aortic aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome","volume":"35","author":"Cook","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.recesp.2011.05.027","article-title":"Variabilidad fenot\u00edpica del s\u00edndrome de Marfan en una familia con una nueva mutaci\u00f3n en el gen FBN1","volume":"65","author":"D\u00edaz de Bustamante","year":"2012","journal-title":"Rev Esp Cardiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1038\/s41431-020-0666-0","article-title":"Is HSPG2 a modifier gene for Marfan syndrome?","volume":"28","author":"Gerdes Gyuricza","year":"2020","journal-title":"Eur J Hum Genet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1093\/hmg\/ddg241","article-title":"Allelic variation in normal human FBN1 expression in a family with Marfan syndrome: a potential modifier of phenotype?","volume":"12","author":"Hutchinson","year":"2003","journal-title":"Hum Mol Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1038\/s41431-018-0164-9","article-title":"Association of modifiers and other genetic factors explain Marfan syndrome clinical variability","volume":"26","author":"Aubart","year":"2018","journal-title":"Eur J Hum Genet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1073\/pnas.77.8.4494","article-title":"Isolation of a heparan sulfate-containing proteoglycan from basement membrane","volume":"77","author":"Hassell","year":"1980","journal-title":"Proc Natl Acad Sci USA"},{"key":"B25","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/15537","article-title":"Perlecan is essential for cartilage and cephalic development","volume":"23","author":"Arikawa-Hirasawa","year":"1999","journal-title":"Nat Genet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"11404","DOI":"10.1074\/jbc.M409882200","article-title":"Microfibrils at basement membrane zones interact with perlecan via fibrillin-1","volume":"280","author":"Tiedemann","year":"2005","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00418-011-0854-7","article-title":"Colocalization in vivo and association in vitro of perlecan and elastin","volume":"136","author":"Hayes","year":"2011","journal-title":"Histochem Cell Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3390\/ijms23010315","article-title":"Increased risk of aortic dissection with perlecan deficiency","volume":"23","author":"Nonaka","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1083\/jcb.147.5.1109","article-title":"Perlecan maintains the integrity of cartilage and some basement membranes","volume":"147","author":"Costell","year":"1999","journal-title":"J Cell Biol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.jss.2006.09.001","article-title":"Mechanics of fresh, refrigerated, and frozen arterial tissue","volume":"139","author":"Stemper","year":"2007","journal-title":"J Surg Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"109462","DOI":"10.1016\/j.jbiomech.2019.109462","article-title":"The effects of \u221280\u00a0\u2218C short-term storage on the mechanical response of tricuspid valve leaflets","volume":"98","author":"Salinas","year":"2020","journal-title":"J Biomech"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1007\/s10439-013-0799-1","article-title":"Biomechanical phenotyping of central arteries in health and disease: advantages of and methods for murine models","volume":"41","author":"Ferruzzi","year":"2013","journal-title":"Ann Biomed Eng"},{"key":"B33","author":"Farra","year":""},{"key":"B34","doi-asserted-by":"publisher","first-page":"100102","DOI":"10.1016\/j.crphys.2023.100102","article-title":"Biomechanical remodeling of the murine descending thoracic aorta during late-gestation pregnancy","volume":"6","author":"Vargas","year":"2023","journal-title":"Curr Res Physiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"H2270","DOI":"10.1152\/ajpheart.00893.2020","article-title":"Structural and functional remodeling of the female Apoe\u00a0\u2212\/\u2212 mouse aorta due to chronic cigarette smoke exposure","volume":"320","author":"Farra","year":"2021","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/0021-9290(83)90080-5","article-title":"Analysis of the passive mechanical properties of rat carotid arteries","volume":"16","author":"Weizs\u00e4cker","year":"1983","journal-title":"J Biomech"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.1016\/j.cma.2006.06.018","article-title":"Theory of small on large: potential utility in computations of fluid\u2013solid interactions in arteries","volume":"196","author":"Baek","year":"2007","journal-title":"Comput Methods Appl Mech Eng"},{"key":"B38","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1126\/science.276.5309.122","article-title":"A general model for the origin of allometric scaling laws in biology","volume":"276","author":"West","year":"1997","journal-title":"Science"},{"key":"B39","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1177\/152660280701400421","article-title":"Increased anterior abdominal aortic wall motion: possible role in aneurysm pathogenesis and design of endovascular devices","volume":"14","author":"Goergen","year":"2007","journal-title":"J Endovasc Ther"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0202123","DOI":"10.1371\/journal.pone.0202123","article-title":"Comparative mechanics of diverse mammalian carotid arteries","volume":"13","author":"Prim","year":"2018","journal-title":"PLoS ONE"},{"key":"B41","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1161\/CIR.0b013e3181d4739e","article-title":"2010 ACCF\/AHA\/AATS\/ACR\/ASA\/SCA\/SCAI\/SIR\/STS\/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"121","author":"Hiratzka","year":"2010","journal-title":"Circulation"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e0230208","DOI":"10.1371\/journal.pone.0230208","article-title":"Prosthetic aortic graft replacement of the ascending thoracic aorta alters biomechanics of the native descending aorta as assessed by transthoracic echocardiography","volume":"15","author":"Palumbo","year":"2020","journal-title":"PLoS ONE"},{"key":"B43","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41572-021-00298-7","article-title":"Marfan syndrome","volume":"7","author":"Milewicz","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B44","doi-asserted-by":"publisher","first-page":"800730","DOI":"10.3389\/fcvm.2021.800730","article-title":"Progressive microstructural deterioration dictates evolving biomechanical dysfunction in the Marfan aorta","volume":"8","author":"Cavinato","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1002\/dvdy.283","article-title":"Developmental origins of mechanical homeostasis in the aorta","volume":"250","author":"Murtada","year":"2021","journal-title":"Dev Dyn"},{"key":"B46","doi-asserted-by":"publisher","first-page":"H44","DOI":"10.1152\/ajpheart.00255.2021","article-title":"Age and sex dependency of thoracic aortopathy in a mouse model of Marfan syndrome","volume":"322","author":"Gharraee","year":"2022","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B47","author":"Weiss","year":""},{"key":"B48","doi-asserted-by":"publisher","first-page":"e002058","DOI":"10.1161\/CIRCGEN.117.002058","article-title":"Impact of pathogenic FBN1 variant types on the progression of aortic disease in patients with Marfan syndrome","volume":"11","author":"Takeda","year":"2018","journal-title":"Circulation"},{"key":"B49","doi-asserted-by":"publisher","first-page":"116073","DOI":"10.1016\/j.bone.2021.116073","article-title":"Hyperkyphosis is not dependent on bone mass and quality in the mouse model of Marfan syndrome","volume":"152","author":"Souza","year":"2021","journal-title":"Bone"},{"key":"B50","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1016\/j.jbiomech.2015.11.059","article-title":"Differential ascending and descending aortic mechanics parallel aneurysmal propensity in a mouse model of Marfan syndrome","volume":"49","author":"Bellini","year":"2016","journal-title":"J Biomech"},{"key":"B51","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s10237-018-1080-1","article-title":"Absence of LTBP-3 attenuates the aneurysmal phenotype but not spinal effects on the aorta in Marfan syndrome","volume":"18","author":"Korneva","year":"2019","journal-title":"Biomech Model Mechanobiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e132","DOI":"10.1161\/ATVBAHA.123.319120","article-title":"FN (fibronectin)-integrin \u03b15 signaling promotes thoracic aortic aneurysm in a mouse model of Marfan syndrome","volume":"43","author":"Chen","year":"2023","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0002-9149(98)00315-4","article-title":"Changes in aortic distensibility and pulse wave velocity assessed with magnetic resonance imaging following beta-blocker therapy in the marfan syndrome","volume":"82","author":"Groenink","year":"1998","journal-title":"Am J Cardiol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.jcmg.2018.03.017","article-title":"Influence of aortic dilation on the regional aortic stiffness of bicuspid aortic valve assessed by 4-dimensional flow cardiac magnetic resonance","volume":"12","author":"Andrea","year":"2019","journal-title":"JACC: Cardiovasc Imaging"},{"key":"B55","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.actbio.2023.03.023","article-title":"Lengthwise regional mechanics of the human aneurysmal ascending thoracic aorta","volume":"162","author":"Tarraf","year":"2023","journal-title":"Acta Biomater"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.amjcard.2018.01.016","article-title":"Influence of aortic stiffness on aortic-root growth rate and outcome in patients with the Marfan syndrome","volume":"121","author":"Selamet Tierney","year":"2018","journal-title":"Am J Cardiol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0002-9149(77)80005-2","article-title":"Pathogenesis of dissecting aneurysm of aorta","volume":"39","author":"Schlatmann","year":"1977","journal-title":"Am J Cardiol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.forsciint.2011.07.006","article-title":"Aortic dissecting aneurysms\u2014histopathological findings","volume":"214","author":"Bode-J\u00e4nisch","year":"2012","journal-title":"Forensic Sci Int"},{"key":"B59","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.jss.2013.06.007","article-title":"Molecular mechanisms of thoracic aortic dissection","volume":"184","author":"Wu","year":"2013","journal-title":"J Surg Res"},{"key":"B60","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.carpath.2016.03.002","article-title":"Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases\u2014nomenclature and diagnostic criteria","volume":"25","author":"Halushka","year":"2016","journal-title":"Cardiovasc Pathol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2019.08.017","article-title":"Biomechanics of aortic wall failure with a focus on dissection and aneurysm: a review","volume":"99","author":"Sherifova","year":"2019","journal-title":"Acta Biomater"},{"key":"B62","doi-asserted-by":"publisher","first-page":"13185","DOI":"10.1038\/s41598-021-92659-1","article-title":"Quantitative not qualitative histology differentiates aneurysmal from nondilated ascending aortas and reveals a net gain of medial components","volume":"11","author":"Yousef","year":"2021","journal-title":"Sci Rep"},{"key":"B63","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.artres.2016.04.001","article-title":"Loss of elastic fiber integrity compromises common carotid artery function: implications for vascular aging","volume":"14","author":"Ferruzzi","year":"2016","journal-title":"Artery Res"},{"key":"B64","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.actbio.2021.07.059","article-title":"Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement","volume":"134","author":"Weiss","year":"2021","journal-title":"Acta Biomater"},{"key":"B65","doi-asserted-by":"publisher","first-page":"031007","DOI":"10.1115\/1.4029431","article-title":"Decreased elastic energy storage, not increased material stiffness, characterizes central artery dysfunction in fibulin-5 deficiency independent of sex","volume":"137","author":"Ferruzzi","year":"2015","journal-title":"J Biomech Eng"},{"key":"B66","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/415168a","article-title":"Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo","volume":"415","author":"Yanagisawa","year":"2002","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"publisher","first-page":"107215","DOI":"10.1016\/j.vph.2023.107215","article-title":"Insights into elastic fiber fragmentation: mechanisms and treatment of aortic aneurysm in Marfan syndrome","volume":"153","author":"Seeburun","year":"2023","journal-title":"Vascul Pharmacol"},{"key":"B68","doi-asserted-by":"publisher","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":"B69","doi-asserted-by":"publisher","first-page":"ehab724.1863","DOI":"10.1093\/eurheartj\/ehab724.1863","article-title":"Morphological and secretory dysfunction of left atrium in Marfan syndrome","volume":"42","author":"Ernst","year":"2021","journal-title":"Eur Heart J"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ajmg.a.30979","article-title":"Severe infantile Marfan syndrome versus neonatal Marfan syndrome","volume":"139","author":"Hennekam","year":"2005","journal-title":"Am J Med Genet A"},{"key":"B71","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1093\/cvr\/cvn225","article-title":"Perlecan is critical for heart stability","volume":"80","author":"Sasse","year":"2008","journal-title":"Cardiovasc Res"},{"key":"B72","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1161\/01.ATV.0000161277.46464.11","article-title":"Partial off-loading of longitudinal tension induces arterial tortuosity","volume":"25","author":"Jackson","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"105849","DOI":"10.3389\/fcell.2022.856261","article-title":"Perlecan, a multi-functional, cell-instructive, matrix-stabilizing proteoglycan with roles in tissue development has relevance to connective tissue repair and regeneration","volume":"10","author":"Hayes","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1146\/annurev-cellbio-100109-104020","article-title":"Assembly of fibronectin extracellular matrix","volume":"26","author":"Singh","year":"2010","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"3107879","DOI":"10.1155\/2016\/3107879","article-title":"Phenotypic and functional changes of endothelial and smooth muscle cells in thoracic aortic aneurysms","volume":"2016","author":"Malashicheva","year":"2016","journal-title":"Int J Vasc Med"},{"key":"B76","doi-asserted-by":"publisher","first-page":"e13697","DOI":"10.1111\/eci.13697","article-title":"The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections","volume":"52","author":"Rombouts","year":"2022","journal-title":"Eur J Clin Invest"},{"key":"B77","doi-asserted-by":"publisher","first-page":"938","DOI":"10.3389\/fphys.2017.00938","article-title":"Thoracic aortic aneurysm development in patients with bicuspid aortic valve: what is the role of endothelial cells?","volume":"8","author":"van de Pol","year":"2017","journal-title":"Front Physiol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1111\/j.1476-5381.2009.00396.x","article-title":"Vasodilator efficacy of nitric oxide depends on mechanisms of intracellular calcium mobilization in mouse aortic smooth muscle cells","volume":"158","author":"Van Hove","year":"2009","journal-title":"Br J Pharmacol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/jemt.20562","article-title":"Novel interactions of perlecan: unraveling perlecan\u2019s role in angiogenesis","volume":"71","author":"Bix","year":"2008","journal-title":"Microsc Res Tech"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e12272","DOI":"10.14814\/phy2.12272","article-title":"Perlecan deficiency causes endothelial dysfunction by reducing the expression of endothelial nitric oxide synthase","volume":"3","author":"Nonaka","year":"2015","journal-title":"Physiol Rep"},{"key":"B81","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/jcp.1094","article-title":"Perlecan inhibits smooth muscle cell adhesion to fibronectin: role of heparan sulfate","volume":"188","author":"Lundmark","year":"2001","journal-title":"J Cell Physiol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ajhg.2017.06.004","article-title":"From peas to disease: modifier genes, network resilience, and the genetics of health","volume":"101","author":"Riordan","year":"2017","journal-title":"Am J Hum Genet"},{"key":"B83","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/ncpcardio0937","article-title":"Etiology, pathogenesis and management of thoracic aortic aneurysm","volume":"4","author":"Ince","year":"2007","journal-title":"Nat Clin Pract Cardiovasc Med"},{"key":"B84","doi-asserted-by":"publisher","first-page":"20170327","DOI":"10.1098\/rsif.2017.0327","article-title":"Differential cell-matrix mechanoadaptations and inflammation drive regional propensities to aortic fibrosis, aneurysm or dissection in hypertension","volume":"14","author":"Bersi","year":"2017","journal-title":"J R Soc Interface"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2024.1319164\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T04:48:47Z","timestamp":1710305327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2024.1319164\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":84,"alternative-id":["10.3389\/fcvm.2024.1319164"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2024.1319164","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"article-number":"1319164"}}