{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:04:30Z","timestamp":1789751070617,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"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>Genetic factors play a significant role in the pathogenesis of mitral valve diseases, including mitral valve prolapse (MVP) and mitral valve regurgitation. Genes like Fibrillin-1 (FBN1), Filamin A (FLNA), matrix metalloproteinase 2 (MMP2), and SRY-box transcription factor 9 (SOX9) are known to influence mitral valve pathology but knowledge of the exact mechanism is far from clear. Data regarding serum parameters, transesophageal echocardiography, and genetic and histopathologic parameters were investigated in 54 patients who underwent cardiovascular surgery for mitral valve regurgitation. The possible association between Fibrillin-1, Filamin A, MMP2, and SOX9 gene expressions was checked in relationship with the parameters of systemic inflammatory response. The mRNA expression levels (RQ\u2014relative quantification) were categorized into three distinct groups: low (RQ &lt; 1), medium\/normal (RQ = 1\u20132), and high (RQ &gt; 2). Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 (p &lt; 0.05). The myxoid degeneration level was associated with the mRNA expression level for FBN1 and a low lymphocyte-monocyte ratio was associated with an increased mRNA expression of FBN1 (p &lt; 0.05). A high number of monocytes was associated with high values of FBN1 whereas the increase in the number of lymphocytes was associated with high levels of MMP2. In addition, we observed that the risk of severe hyalinization was enhanced by a low mRNA expression of FLNA and\/or SOX9. In conclusion, a lower FLNA mRNA expression can reflect the aging process that is highlighted in mitral valve pathology as a higher risk for hyalinization, especially in males, that might be prevented by upregulation of the SOX9 gene. FBN1 and MMP2 influence the inflammation-related fibrotic degeneration of the mitral valve. Understanding the genetic base of mitral valve pathology can provide insights into disease mechanisms, risk stratification, and potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms25179410","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T09:39:32Z","timestamp":1725010772000},"page":"9410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Significance of Fibrillin-1, Filamin A, MMP2 and SOX9 in Mitral Valve Pathology"],"prefix":"10.3390","volume":"25","author":[{"given":"Carmen Elena","family":"Opris","sequence":"first","affiliation":[{"name":"Department of Adult and Children Cardiovascular Recovery, Emergency Institute for Cardio-Vascular Diseases and Transplantation, 540139 Targu Mures, Romania"},{"name":"Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horatiu","family":"Suciu","sequence":"additional","affiliation":[{"name":"Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"},{"name":"Romanian Academy of Medical Sciences, 030173 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioan","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"},{"name":"Romanian Academy of Medical Sciences, 030173 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanziana","family":"Flamand","sequence":"additional","affiliation":[{"name":"Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius Mihai","family":"Harpa","sequence":"additional","affiliation":[{"name":"Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin Ioan","family":"Opris","sequence":"additional","affiliation":[{"name":"Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Popa","sequence":"additional","affiliation":[{"name":"Faculty of European Studies, Babes-Bolyai University, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Environmental Chemistry, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, 540139 Targu Mures, Romania"},{"name":"Research Center for Oncopathology and Translational Medicine (CCOMT), George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-5118","authenticated-orcid":false,"given":"Simona","family":"Gurzu","sequence":"additional","affiliation":[{"name":"Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"},{"name":"Romanian Academy of Medical Sciences, 030173 Bucharest, Romania"},{"name":"Research Center for Oncopathology and Translational Medicine (CCOMT), George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: A population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1161\/CIRCULATIONAHA.118.034075","article-title":"Mitral Valve Prolapse, Ventricular Arrhythmias, and Sudden Death","volume":"140","author":"Basso","year":"2019","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"155535","DOI":"10.1016\/j.prp.2024.155535","article-title":"Update on the genetic profile of mitral valve development and prolapse","volume":"262","author":"Opris","year":"2024","journal-title":"Pathol. 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