Department of Adult and Children Cardiovascular Recovery, Emergency Institute for Cardio-Vascular Diseases and Transplantation, 540139 Targu Mures, Romania.
Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 Targu Mures, Romania.
Int J Mol Sci. 2024 Aug 29;25(17):9410. doi: 10.3390/ijms25179410.
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-relative quantification) were categorized into three distinct groups: low (RQ < 1), medium/normal (RQ = 1-2), and high (RQ > 2). Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 ( < 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 ( < 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 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.
遗传因素在二尖瓣疾病的发病机制中起重要作用，包括二尖瓣脱垂（MVP）和二尖瓣反流。已知像原纤维蛋白 1（FBN1）、细丝蛋白 A（FLNA）、基质金属蛋白酶 2（MMP2）和性决定区 Y 框转录因子 9（SOX9）等基因影响二尖瓣病理，但确切的机制知之甚少。对 54 名因二尖瓣反流而行心血管手术的患者进行了血清参数、经食管超声心动图以及遗传和组织病理学参数的研究。检查了原纤维蛋白 1、细丝蛋白 A、MMP2 和 SOX9 基因表达与全身炎症反应参数之间的可能关联。mRNA 表达水平（RQ-相对定量）分为三个不同组：低（RQ < 1）、中/正常（RQ = 1-2）和高（RQ > 2）。二尖瓣严重纤维化表现为 FBN1 高表达和 MMP2 低表达（<0.05）。粘液样变性程度与 FBN1 的 mRNA 表达水平相关，淋巴细胞-单核细胞比值低与 FBN1 的 mRNA 表达增加相关（<0.05）。单核细胞数量增加与 FBN1 值升高相关，而淋巴细胞数量增加与 MMP2 水平升高相关。此外，我们观察到 FLNA 和/或 SOX9 的 mRNA 表达降低与严重玻璃样变的风险增加相关。总之，FLNA mRNA 表达降低可反映二尖瓣病变中强调的老化过程，即玻璃样变的风险增加，尤其是男性，通过上调该基因可能预防。FBN1 和 MMP2 影响与炎症相关的二尖瓣纤维化变性。了解二尖瓣病理的遗传基础可以深入了解疾病机制、风险分层和潜在的治疗靶点。
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