Li Y Y, Feng Y, McTiernan C F, Pei W, Moravec C S, Wang P, Rosenblum W, Kormos R L, Feldman A M
Cardiovascular Institute, Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Circulation. 2001 Sep 4;104(10):1147-52. doi: 10.1161/hc3501.095215.
Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates.
LV samples were collected from patients with dilated cardiomyopathy (DCM, n=14) or ischemic cardiomyopathy (ICM, n=16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support.
The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insoluble to total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support.
左心室辅助装置（LVAD）对衰竭心脏的支持可引起心肌结构和功能的有益改变。基质金属蛋白酶（MMPs）在衰竭心脏中增加，并且在体外可被心肌细胞的牵张所诱导。我们假设机械卸载可能通过调节MMPs及其底物来影响左心室的可塑性。
在植入LVAD时以及心脏移植期间，从扩张型心肌病（DCM，n = 14）或缺血性心肌病（ICM，n = 16）患者中采集左心室样本。通过酶联免疫吸附测定法（ELISA）检测MMP - 1、- 3和- 9，通过明胶酶谱法检测MMP - 2和- 9的明胶分解活性，通过蛋白质免疫印迹法检测金属蛋白酶组织抑制剂（TIMPs）。通过胃蛋白酶溶解分离总可溶性和不溶性胶原蛋白，并通过羟脯氨酸定量测定其含量。通过Sircol胶原蛋白测定法测量未变性的可溶性胶原蛋白。结果显示，LVAD支持后，MMP - 1和- 9降低，而TIMP - 1和- 3升高，但MMP - 2和- 3以及TIMP - 2和- 4无变化。未变性胶原蛋白增加，LVAD支持后，ICM中未变性与总可溶性胶原蛋白的比例增加，DCM中不溶性与总可溶性胶原蛋白的比例增加。
LVAD支持后MMPs降低、TIMPs升高以及未变性与总可溶性胶原蛋白和不溶性与总可溶性胶原蛋白的比例增加，表明MMP活性降低减少了对基质的损伤。这些变化可能有助于LVAD支持后的功能恢复和左心室可塑性。
