cleavage-resistant胶原蛋白突变对左心室重构的影响。

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林赛ML,吉冈J,麦吉利弗雷C, Muangman年代,甘农J, Verghese, Aikawa M,利比P,奎恩SM,李RT

cleavage-resistant胶原蛋白突变对左心室重构的影响。

保监会研究》2003年8月8日,93 (3):238 - 45。Epub 2003 7月10。

PubMed ID

12855673 (在PubMed

]

文摘

矩阵metalloproteinase-mediated I型胶原蛋白的降解可能发挥作用在心脏重塑紧张或损伤。探索这一假设,我们使用纯合子小鼠(r / r)目标在Col1a1基因突变;这些老鼠合成胶原蛋白我抗胶原酶在Gly975-Leu976乳沟。64 r / r和84年同窝出生仔畜野生型小鼠(WT)进行了实验压力过载横向主缢痕(TAC)或心肌梗死(MI)。超声心动图、血流动力学和组织学参数进行评估后12周TAC或MI后21天。TAC在4周后,胶原蛋白水平,壁厚和超声心动图参数两组相似。TAC在12周后,r / r小老鼠LV维度(WT ESD: 2.7 + / - -0.2毫米和1.7 + / - -0.2毫米r / r, P < 0.013;WT EDD: 3.8 + / - -0.2毫米和3.1 + / - -0.1毫米r / r, P < 0.013);更好的分数缩短(30 + / WT与46 + -2% / -4% r / r;P < 0.013);和更低的LV /体重比值(7.3 + / - -0.6 WT和5.1 + / - -0.5 r / r; P<0.013). Surprisingly, these differences were not accompanied by differences in collagen accumulation, myocyte cross-sectional areas, wall thickness, or microvessel densities. Furthermore, no differences in LV remodeling assessed by echocardiography, fibrosis, or hemodynamic parameters were found between r/r and WT mice after MI. Thus, a mutation that encodes a collagenase cleavage-resistant collagen I does not affect early LV remodeling after TAC or MI, suggesting that collagen cleavage at this site is not the mechanism by which metalloproteinases mediate LV remodeling. Collagen cleavage could, however, have a role in preservation of cardiac function in late remodeling by mechanisms independent of collagen accumulation. We were not able to detect collagen cleavage fragments, and could not, therefore, rule out the possibility of collagen cleavage at additional sites.

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药物靶点

药物	目标	类	生物	药理作用	行动
胶原酶histolyticum梭状芽胞杆菌	胶原蛋白alpha - (I)链	蛋白质	人类	是的	粘结剂	细节