Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation.
Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation.
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DOI：
10.3390/jcdd8080092
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发表时间：
2021-08-04
影响因子：
2.4
通讯作者：
Kern CB
中科院分区：
文献类型：
--
作者：
Kern CB
二叶式主动脉瓣（BAV）是最常见的心脏畸形，在0.5%至2%的人群中发现。BAV存在于约50%的重度主动脉瓣狭窄患者中，并且是主动脉瘤的独立风险因素。目前，没有治疗BAV的疗法，迄今为止鉴定的人类突变代表了相对少量的BAV患者。然而，在越来越多的转基因小鼠中发现BAV正在推进我们对BAV形成的分子途径的理解。在这项研究中，我们利用小鼠模型之间的BAV表型特征的比较作为一种工具，以推进我们对BAV形成的理解。小鼠BAV数据的整理表明，在临时细胞外基质（P-ECM）中过量的多功能蛋白聚糖是BAV发育的共同因素。虽然在许多鼠BAV模型中BAV的百分比较低，但剩余的突变小鼠表现出更大和更无定形的三尖瓣AoV，与同窝小鼠相比也具有过量的P-ECM。在鼠BAV模型中识别共同的分子特征可能导致BAV治疗靶点和疾病进展的生物标志物，用于这种高度流行和异质性心血管畸形。
A bicuspid aortic valve (BAV) is the most common cardiac malformation, found in 0.5% to 2% of the population. BAVs are present in approximately 50% of patients with severe aortic stenosis and are an independent risk factor for aortic aneurysms. Currently, there are no therapeutics to treat BAV, and the human mutations identified to date represent a relatively small number of BAV patients. However, the discovery of BAV in an increasing number of genetically modified mice is advancing our understanding of molecular pathways that contribute to BAV formation. In this study, we utilized the comparison of BAV phenotypic characteristics between murine models as a tool to advance our understanding of BAV formation. The collation of murine BAV data indicated that excess versican within the provisional extracellular matrix (P-ECM) is a common factor in BAV development. While the percentage of BAVs is low in many of the murine BAV models, the remaining mutant mice exhibit larger and more amorphous tricuspid AoVs, also with excess P-ECM compared to littermates. The identification of common molecular characteristics among murine BAV models may lead to BAV therapeutic targets and biomarkers of disease progression for this highly prevalent and heterogeneous cardiovascular malformation.
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DOI：
10.1002/dvdy.24435
发表时间：
2016-10
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Dupuis LE;Doucette L;Rice AK;Lancaster AE;Berger MG;Chakravarti S;Kern CB
通讯作者：
Kern CB
影响因子：
2.7
作者：
Dupuis LE;McCulloch DR;McGarity JD;Bahan A;Wessels A;Weber D;Diminich AM;Nelson CM;Apte SS;Kern CB
通讯作者：
Kern CB
影响因子：
2.5
作者：
Cooley, Marion A.;Fresco, Victor M.;Dorlon, Margaret E.;Twal, Waleed O.;Lee, Nathan V.;Barth, Jeremy L.;Kern, Christine B.;Iruela-Arispe, M. Luisa;Argraves, W. Scott
通讯作者：
Argraves, W. Scott
DOI：
10.1161/atvbaha.119.313077
发表时间：
2019-10-01
影响因子：
8.7
作者：
Dupuis, Loren E.;Nelson, E. Lockett;Kern, Christine B.
通讯作者：
Kern, Christine B.
影响因子：
29.4
作者：
Garg P;Jeppsson S;Dalmasso G;Ghaleb AM;McConnell BB;Yang VW;Gewirtz AT;Merlin D;Sitaraman SV
通讯作者：
Sitaraman SV