Versican proteolysis mediates myocardial. regression during outflow tract development
Versican proteolysis mediates myocardial. regression during outflow tract development
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DOI：
10.1002/dvdy.21059
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发表时间：
2007-03-01
影响因子：
2.5
通讯作者：
Mjaatvedt, Corey H.
中科院分区：
文献类型：
--
作者：
Kern, Christine B.;Norris, Russell A.;Mjaatvedt, Corey H.
心脏流出道（OFT）形成的一个重要阶段是共同出口远端区域的重塑，其中心肌袖被平滑肌取代。在这里，我们表明，蛋白多糖多功能蛋白聚糖的表达减少前，从远端心脏出口心肌损失伴随着多功能蛋白聚糖的N-末端切割片段的生产增加。为了测试多功能蛋白聚糖蛋白水解是否在OFT重塑中起作用，我们确定了腺病毒介导的缺乏已知基质金属蛋白酶切割位点（V3）和多功能蛋白聚糖N-末端片段（G1）的多功能蛋白聚糖亚型表达的影响。V3表达促进了近端OFT心肌层厚度的增加，而与增殖无关。相反，G1域引起OFT心肌变薄和中断。这些在体内的研究结果是一致的，使用培养的原代心肌细胞显示，V3促进心肌细胞-细胞的协会，而G1域引起的损失心肌细胞-细胞的协会。两者合计，我们得出结论，完整的多功能蛋白聚糖和G1多功能蛋白聚糖裂解产物对心肌细胞有相反的影响，多功能蛋白聚糖蛋白水解可能会促进远端心肌的损失在OFT重塑。
An important phase of cardiac outflow tract (OFT) formation is the remodeling of the distal region of the common outlet in which the myocardial sleeve is replaced by with smooth muscle. Here we demonstrate that expression of the proteoglycan versican is reduced before the loss of myocardium from the distal cardiac outlet concomitant with an increase in production of the N-terminal cleavage fragment of versican. To test whether versican proteolysis plays a role in OFT remodeling, we determined the effects of adenoviral-mediated expression of a versican isoform devoid of known matrix metalloproteinase cleavage sites (V3) and an N-terminal fragment of versican (G1). V3 expression promoted an increase in thickness of the proximal OFT myocardial layer independent of proliferation. In contrast, the G1 domain caused thinning and interruptions of the OFT myocardium. These in vivo findings were consistent with findings using cultured primary cardiomyocytes showing that the V3 promoted myocardial cell-cell association while the G1 domain caused a loss of myocardial cell-cell association. Taken together, we conclude that intact versican and G1-containing versican cleavage products have opposing effects on myocardial cells and that versican proteolysis may facilitate the loss of distal myocardium during OFT remodeling.