{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T19:48:15Z","timestamp":1765828095609,"version":"3.40.5"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CEVA Sant\u00e9 Animale"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Animals<\/jats:title>\n<jats:p>We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL\/6J and investigated a contribution of the serotonergic system.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Males and females FVB\/NJ and FVB\/NRj were compared to the putative C57BL\/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-\u03b21 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT<jats:sub>2A<\/jats:sub> and 5-HT<jats:sub>2B<\/jats:sub> receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared to C57BL\/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-\u03b21 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0257022","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T18:14:24Z","timestamp":1630606464000},"page":"e0257022","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of the spontaneous degenerative mitral valve disease in FVB mice"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-3803","authenticated-orcid":true,"given":"Estelle","family":"Ayme-Dietrich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghina 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myxomatous change in Harlan Sprague-Dawley rats (Hsd:S-D) and CD-1 mice: its microscopic resemblance to drug-induced valvulopathy in humans","volume":"30","author":"CS Elangbam","year":"2002","journal-title":"Toxicol Pathol."},{"issue":"5","key":"pone.0257022.ref002","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1369\/jhc.4A6500.2005","article-title":"5-Hydroxytryptamine (5HT) receptors in the heart valves of cynomolgus monkeys and Sprague-Dawley rats","volume":"53","author":"CS Elangbam","year":"2005","journal-title":"J Histochem Cytochem"},{"issue":"2\u20133","key":"pone.0257022.ref003","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.etp.2006.08.001","article-title":"Evaluation of glycosaminoglycans content and 5-hydroxytryptamine 2B receptor in the heart valves of Sprague-Dawley rats with spontaneous mitral valvulopathy\u2014a possible exacerbation by dl-amphetamine sulfate in Fischer 344 rats?","volume":"58","author":"CS 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Lindner","year":"2021","journal-title":"Methods."},{"key":"pone.0257022.ref007","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ymeth.2021.04.001","article-title":"Droplet digital PCR or quantitative PCR for in-depth genomic and functional validation of genetically altered rodents","volume":"191","author":"L Lindner","year":"2021","journal-title":"Methods"},{"issue":"8","key":"pone.0257022.ref008","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/clinchem\/hvaa125","article-title":"The Digital MIQE Guidelines Update: Minimum Information for Publication of Quantitative Digital PCR Experiments for 2020","volume":"66","author":"Huggett JF dMIQE Group","year":"2020","journal-title":"Clin Chem"},{"issue":"22","key":"pone.0257022.ref009","doi-asserted-by":"crossref","first-page":"4123","DOI":"10.1111\/bph.13981","article-title":"The role of 5-HT2B receptors in mitral valvulopathy: bone marrow mobilization of endothelial progenitors","volume":"174","author":"E Ayme-Dietrich","year":"2017","journal-title":"Br J Pharmacol"},{"issue":"7","key":"pone.0257022.ref010","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11886-019-1145-5","article-title":"Mitral Valve Pathology","volume":"21","author":"GA Fishbein","year":"2019","journal-title":"Curr Cardiol Rep."},{"issue":"4","key":"pone.0257022.ref011","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.carpath.2008.05.001","article-title":"Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves","volume":"18","author":"V Gupta","year":"2009","journal-title":"Cardiovasc Pathol."},{"issue":"1","key":"pone.0257022.ref012","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jvc.2012.02.001","article-title":"Pathology of myxomatous mitral valve disease in the dog","volume":"14","author":"PR Fox","year":"2012","journal-title":"J Vet Cardiol."},{"issue":"4","key":"pone.0257022.ref013","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1055\/s-2007-1020319","article-title":"Early alteration of bioprosthetic cardiac valves in sheep: influence of the immunological status","volume":"37","author":"G Noera","year":"1989","journal-title":"Thorac Cardiovasc Surg."},{"key":"pone.0257022.ref014","first-page":"212","article-title":"Eosinophils and endomyocardial fibrosis","volume":"7","author":"CJ Spry","year":"1983","journal-title":"Contrib Microbiol Immunol"},{"issue":"1","key":"pone.0257022.ref015","doi-asserted-by":"crossref","first-page":"165569","DOI":"10.1016\/j.bbadis.2019.165569","article-title":"Differential metabolic and multi-tissue transcriptomic responses to fructose consumption among genetically diverse mice","author":"G Zhang","year":"2020","journal-title":"Biochim Biophys Acta Mol Basis 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Dis"},{"issue":"5","key":"pone.0257022.ref019","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/jvim.12420","article-title":"Serotonin concentrations in platelets, plasma, mitral valve leaflet, and left ventricular myocardial tissue in dogs with myxomatous mitral valve disease","volume":"28","author":"SE Cremer","year":"2014","journal-title":"J Vet Intern Med"},{"issue":"5","key":"pone.0257022.ref020","first-page":"626","article-title":"Organ culture as a tool to identify early mechanisms of serotonergic valve disease","volume":"19","author":"JE Barzilla","year":"2010","journal-title":"J Heart Valve Dis"},{"issue":"3","key":"pone.0257022.ref021","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.carpath.2011.07.005","article-title":"Elevated cyclic stretch and serotonin result in altered aortic valve remodeling via a mechanosensitive 5-HT(2A) receptor-dependent pathway","volume":"21","author":"K Balachandran","year":"2012","journal-title":"Cardiovasc Pathol."},{"issue":"6","key":"pone.0257022.ref022","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1124\/mol.63.6.1223","article-title":"3,4-methylenedioxymethamphetamine (MDMA, \u201cEcstasy\u201d) induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro","volume":"63","author":"V Setola","year":"2003","journal-title":"Mol Pharmacol"},{"issue":"9","key":"pone.0257022.ref023","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.amjcard.2007.06.045","article-title":"Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease","volume":"100","author":"S Droogmans","year":"2007","journal-title":"Am J Cardiol"},{"issue":"15","key":"pone.0257022.ref024","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1093\/eurheartj\/ehr089","article-title":"Quadruple valve replacement for valve destruction in carcinoid heart disease","volume":"32","author":"E McAlindon","year":"2011","journal-title":"Eur Heart J"},{"key":"pone.0257022.ref025","doi-asserted-by":"crossref","first-page":"107196","DOI":"10.1016\/j.carpath.2019.107196","article-title":"Comparative pathology of human and canine myxomatous mitral valve degeneration: 5HT and TGF-\u03b2 mechanisms","volume":"46","author":"MA Oyama","year":"2020","journal-title":"Cardiovasc Pathol."},{"issue":"1","key":"pone.0257022.ref026","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1161\/CIRCRESAHA.108.180976","article-title":"Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy","volume":"104","author":"F Jaffr\u00e9","year":"2009","journal-title":"Circ Res"},{"issue":"3","key":"pone.0257022.ref027","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s002130100694","article-title":"Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice","volume":"155","author":"I Lucki","year":"2001","journal-title":"Psychopharmacology (Berl)"},{"issue":"6","key":"pone.0257022.ref028","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1152\/japplphysiol.00117.2011","article-title":"Differences in serotoninergic metabolism possibly contribute to differences in breathing phenotype of FVB\/N and C57BL\/6J mice","volume":"110","author":"C Menuet","year":"2011","journal-title":"J Appl Physiol (1985)"},{"issue":"2","key":"pone.0257022.ref029","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1601-183X.2008.00452.x","article-title":"Social approach in genetically engineered mouse lines relevant to autism","volume":"8","author":"SS Moy","year":"2009","journal-title":"Genes Brain Behav"},{"issue":"38","key":"pone.0257022.ref030","doi-asserted-by":"crossref","first-page":"20210","DOI":"10.1074\/jbc.M116.736983","article-title":"Loss of Serotonin Transporter Function Alters ADP-mediated Glycoprotein \u03b1IIb\u03b23 Activation through Dysregulation of the 5-HT2A Receptor","volume":"291","author":"KH Oliver","year":"2016","journal-title":"J Biol Chem"},{"issue":"1\u20132","key":"pone.0257022.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000506744","article-title":"Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review","volume":"111","author":"A Buchanan-Hughes","year":"2021","journal-title":"Neuroendocrinology"},{"issue":"6","key":"pone.0257022.ref032","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/01902140802093204","article-title":"Murine pulmonary response to chronic hypoxia is strain specific","volume":"34","author":"Y Tada","year":"2008","journal-title":"Exp Lung Res"},{"issue":"1","key":"pone.0257022.ref033","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/cvr\/cvs238","article-title":"Developmental basis for filamin-A-associated myxomatous mitral valve disease","volume":"96","author":"K Sauls","year":"2012","journal-title":"Cardiovasc Res"},{"issue":"6","key":"pone.0257022.ref034","doi-asserted-by":"crossref","first-page":"H2480","DOI":"10.1152\/ajpheart.91431.2007","article-title":"Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult","volume":"294","author":"RB Hinton","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"}],"container-title":["PLOS 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