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一个矩阵金属蛋白酶诱导/激活系统存在于人类左心室肌肉中,并且在心力衰竭中被上调
F G Spinale1, M L Coker, L J Heung
1Medical University of South Carolina, Charleston 29425, USA.
Circulation
|October 18, 2000
概括
矩阵金属蛋白酶 (MMPs) 和它们的诱导剂 (EMMPRIN,MT1-MMP) 在扩张性心肌病 (DCM) 的心力衰竭中被上调. 在左心室中准这些MMP为DCM提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 生物化学 生物化学
背景情况:
- 矩阵金属蛋白酶 (MMPs) 是疾病期间矩阵重塑的关键,包括瘤转移.
- 细胞外矩阵金属蛋白酶诱导剂 (EMMPRIN) 和膜型MMP (MT1-MMP) 都与MMP调节有关.
- 在扩张性心肌病 (DCM) 中,EMMPRIN和MT1-MMP在人类左心室 (LV) 心肌中的表达和活性在很大程度上仍然没有特征.
研究的目的:
- 为了研究EMMPRIN和MT1-MMP在人类LV心肌中的表达.
- 评估EMMPRIN和MT1-MMP与MMP在DCM中的活性和表达的关联.
- 探索失败的人类心脏中的潜在治疗点.
主要方法:
- 来自非缺血性和缺血性DCM患者的LV心肌组织的分析,以及正常对照.
- 淋巴镜检查以评估MMP活动.
- 对MMP,EMMPRIN和MT1-MMP表达水平进行定量分析.
主要成果:
- 与正常对照者相比,MMP活性在LV心肌中在非缺血性和缺血性DCM中显著升高 (>2倍).
- 在DCM中,MMP-9,MMP-2和MMP-3的丰度增加,而MMP-1水平下降.
- 在两组DCM中,EMMPRIN表达增加了> 250%,MT1-MMP增加了> 1000%.
结论:
- 扩张性心肌病症的特点是增加LV心肌MMP活性和选择性MMP上调.
- 一个局部的MMP诱导/激活系统涉及EMMPRIN和MT1-MMP存在,并且在失败的人类LV肌细胞中进行上调.
- 调节MMP激活和表达在衰竭的人类LV心肌中,为DCM提供了一个新的治疗途径.
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