Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices
Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices
复制标题
DOI：
10.1161/hc3501.095215
复制
发表时间：
2001-09-04
期刊：
影响因子：
37.8
通讯作者：
Feldman, AM
中科院分区：
文献类型：
--
作者：
Li, YY;Feng, YQ;Feldman, AM
背景-左心辅助装置(LVAD)对衰竭心脏的支持会导致心肌结构和功能的有益变化。基质金属蛋白酶(MMPs)在心力衰竭时升高，并在体外培养的心肌细胞中被牵张诱导。我们假设机械卸载可能通过调节MMPs及其底物来影响LV可塑性。方法和结果：LV标本来自扩张型心肌病(DCM，n=14)和缺血性心肌病(ICM，n=16)患者在植入LVEAD时和心脏移植期间再次采集的LV样本。明胶酶谱法检测明胶酶溶活性，免疫印迹法检测基质金属蛋白酶组织抑制物(TIMPs)。用胃酶增溶的方法分离总的可溶性和不溶性胶原蛋白，并用羟脯氨酸定量测定其含量。用Sirol胶原法测定未变性的可溶性胶原。结果显示，LVAD支持后，MMP1和TIMP-9降低，TIMP-1和TIMP-3升高，而MMP2和TIMP-2和TIMP-2和TIMP-4无明显变化。LVAD支持后，ICM中未变性胶原含量增加，不溶性胶原含量增加，DCM中不溶性胶原含量增加。结论：LVAD支持后基质中MMPs减少，TIMPs增加，未变性胶原和不溶性胶原含量增加，提示基质金属蛋白酶活性降低，对基质的损伤减轻。这些变化可能有助于LVAD支持术后功能的恢复和左心室的可塑性。
Background-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.Methods and Results-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.Conclusions-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.