Cardiac transgenic matrix metalloproteinase-2 expression induces myxomatous valve degeneration: a potential model of mitral valve prolapse disease.
Cardiac transgenic matrix metalloproteinase-2 expression induces myxomatous valve degeneration: a potential model of mitral valve prolapse disease.
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DOI：
10.1016/j.carpath.2008.08.001
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发表时间：
2009-09
影响因子：
3.7
通讯作者：
Lovett, David H.
中科院分区：
文献类型：
--
作者：
Mahimkar, Rajeev;Nguyen, Anita;Mann, Michael;Yeh, Che-Chung;Zhu, Bo-Qing;Karliner, Joel S.;Lovett, David H.
关键词：
粘液瘤性二尖瓣“变性”伴脱垂（MVP）是非缺血性二尖瓣疾病最常见的形式。在粘液瘤性瓣膜中，间质细胞表达细胞外基质降解酶，并且已经假定基质金属蛋白酶（MMPs）促成这些变化。我们产生了在α-肌球蛋白重链启动子控制下具有组成性活性MMP-2的心脏特异性表达的小鼠。这些小鼠在4-6月龄时是正常的;在12-14月龄时，二尖瓣和腱索表现出严重的粘液瘤样变化，超声心动图MVP。主动脉瓣中的粘液瘤性变化也较明显，但程度较轻。粘液瘤性变化是异质性的，仅限于心脏左侧，纤维板内胶原束严重紊乱。阿辛蓝/PAS染色的瓣膜显示在海绵层内大量积累酸性糖胺聚糖，与瓣膜间质细胞分化为软骨细胞表型一致。在腱索和二尖瓣乳头肌尖端发现具有肥大软骨细胞组织学特征的细胞。这份报告表明，一个单一的酶，MMP-2的活性增加，在转基因背景下再现了人类MVP综合征的许多功能。心脏特异性MMP-2转基因小鼠可能提供了一个独特的实验平台，用于评估基于这种疾病的潜在病理生理学的非手术治疗。爱思唯尔公司出版
Myxomatous mitral valve “degeneration” with prolapse (MVP) is the most frequent form of nonischemic mitral valve disease. In myxomatous valves, interstitial cells express extracellular matrix-degrading enzymes and it has been postulated that matrix metalloproteinases (MMPs) contribute to these changes. We generated mice with cardiac-specific expression of constitutively active MMP-2 under the control of the α-myosin heavy chain promoter. These mice are normal at 4–6 months of age; at 12–14 months the mitral valves and chordae tendineae exhibit severe myxomatous change with echocardiographic MVP. Myxomatous change was also evident to a lesser extent in the aortic valves. Myxomatous changes were heterogeneous and limited to the left side of the heart with major disorganization of collagen bundles within the lamina fibrosa. Alcian blue/PAS-stained valves revealed massive accumulation of acidic glycosoaminoglycans within the lamina spongiosa, consistent with valvular interstitial cell differentiation to a chondrocytic phenotype. Cells with the histologic features of hypertrophied chondrocytes were found within the chordae tendineae and the tips of the mitral papillary muscles. This report demonstrates that increased activity of a single enzyme, MMP-2, within a transgenic context reproduces many of the features of the human MVP syndrome. The cardiac-specific MMP-2 transgenic mouse potentially provides a unique experimental platform for the evaluation of nonsurgical therapies based on the underlying pathophysiology of this disease. Published by Elsevier Inc.
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DOI：
10.1016/s0735-1097(03)00626-0
发表时间：
2003-07-16
影响因子：
24
作者：
Grande-Allen, KJ;Griffin, BP;Vesely, I
通讯作者：
Vesely, I
影响因子：
3.3
作者：
Akiyama, K;Hirota, J;Tsuda, M
通讯作者：
Tsuda, M
影响因子：
3.5
作者：
Mosig, Rebecca A.;Dowling, Oonagh;Martignetti, John A.
通讯作者：
Martignetti, John A.
影响因子：
37.8
作者：
KING, BD;CLARK, MA;WOOLEY, CF
通讯作者：
WOOLEY, CF
影响因子：
4.1
作者：
Ashworth, JL;Murphy, G;Kielty, CM
通讯作者：
Kielty, CM