Expression and complex formation of MMP9, MMP2, NGAL, and TIMP1 in porcine myocardium but not in skeletal muscles in male pigs with tachycardia-induced systolic heart failure.
Expression and complex formation of MMP9, MMP2, NGAL, and TIMP1 in porcine myocardium but not in skeletal muscles in male pigs with tachycardia-induced systolic heart failure.
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DOI：
10.1155/2013/283856
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发表时间：
2013
影响因子：
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通讯作者：
Ponikowski P
中科院分区：
文献类型：
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作者：
Kiczak L;Tomaszek A;Bania J;Paslawska U;Zacharski M;Noszczyk-Nowak A;Janiszewski A;Skrzypczak P;Ardehali H;Jankowska EA;Ponikowski P
基质金属蛋白酶（MMPs）参与各种组织中细胞外基质的重塑。它们的功能可能与复合物的形成有关，复合物含有MMP 9、MMP 2、金属蛋白酶1型组织抑制剂（TIMP 1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）。这种复合物在心肌或骨骼肌中都没有研究过。我们检查了20只心力衰竭（HF）的雄性猪和5只假手术动物。在患病和健康动物之间，无论是左心室（LV）心肌还是骨骼肌中，MMP 9、MMP 2、TIMP 1和NGAL的mRNA表达均无差异。在非还原和非变性条件下，我们证明了在患病和健康动物的LV中存在高分子量（HMW）复合物（130、170和220 kDa），含有MMP 9、TIMP 1和NGAL（也是220 kDa复合物中的MMP 2），没有蛋白水解活性，和具有蛋白水解活性的115 kDa MMP 9形式以及72和68 kDa条带（proMMP 2和MMP 2）。蛋白水解活性条带也从HMW复合物中自发释放。在患病和健康动物的骨骼肌中，在非还原和非变性条件下，我们没有发现HMW复合物，蛋白水解活性与72和68 kDa条带（proMMP 2和MMP 2）的存在相关。
Matrix metalloproteinases (MMPs) are involved in the remodeling of extracellular matrix in various tissues. Their functioning could be related to the formation of complexes, containing MMP9, MMP2, tissue inhibitor of metalloproteinases type 1 (TIMP1), and neutrophil gelatinase-associated lipocalin (NGAL). Such complexes have not been investigated in either myocardial or skeletal muscles. We examined 20 male pigs with heart failure (HF), and 5 sham-operated animals. There were no differences in the mRNA expression of MMP9, MMP2, TIMP1, and NGAL between diseased and healthy animals, in either left ventricle (LV) myocardium or skeletal muscles. In LV from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we demonstrated the presence of high molecular weight (HMW) complexes (130, 170, and 220 kDa) containing MMP9, TIMP1, and NGAL (also MMP2 in 220 kDa complex) without proteolytic activity, and a proteolytically active 115 kDa MMP9 form together with 72 and 68 kDa bands (proMMP2 and MMP2). Proteolytically active bands were also spontaneously released from HMW complexes. In skeletal muscles from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we found no HMW complexes, and proteolytic activity was associated with the presence of 72 and 68 kDa bands (proMMP2 and MMP2).