Preload induces troponin I degradation independently of myocardial ischemia.
Preload induces troponin I degradation independently of myocardial ischemia.
复制标题
预负荷诱导肌钙蛋白 I 降解，与心肌缺血无关。
DOI：
10.1161/01.cir.103.16.2035
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发表时间：
2001
期刊：
影响因子：
37.8
通讯作者：
CantyJr,JM
中科院分区：
文献类型：
--
作者：
Feng,J;Schaus,BJ;Fallavollita,JA;Lee,TC;CantyJr,JM
背景：虽然全脑缺血可导致肌钙蛋白I(TnI)降解，但局部缺血不能。我们假设这种差异与预负荷诱导的蛋白分解有关，这种蛋白分解是处于缺血风险的心肌量的函数。方法和结果-分离的大鼠心脏在受控的预负荷水平下进行缓冲灌流。在没有缺血的情况下，将前负荷增加到25毫米汞柱会导致显著的TnI降解(27 kDa比31 kDa条带：16.4±3.6%比4.7±1.9%，P<；0.05)。用25μ摩尔/L钙肽(4.3±0.6%)阻断内源性钙蛋白酶的激活，可阻断TnI的降解。功能得到改善，左心室收缩压从103±4 mm Hg升至137±7 mm Hg(P<；0.05)。消除全脑缺血诱导的顿抑后前负荷的升高也可以防止TnI的降解。结论：Calain介导的TNI蛋白分解可以从顿抑中分离出来，并且是由于前负荷的升高而不是缺血引起的。这增加了持续的预负荷诱导的TnI降解可能长期损害心肌功能的可能性。
Background—Although global ischemia induces troponin I (TnI) degradation, regional ischemia does not. We hypothesized that this disparity is related to preload-induced proteolysis, which varies as a function of the amount of myocardium at risk of ischemia.Methods and Results—Isolated rat hearts were buffer-perfused at controlled levels of preload. Increasing preload to 25 mm Hg in the absence of ischemia produced pronounced TnI degradation (27 kDa versus 31 kDa bands: 16.4±3.6% versus 4.7±1.9% in immediately excised controls,P<0.05). TnI degradation could be blocked by preventing the activation of endogenous calpains with 25 μmol/L calpeptin (4.3±0.6%). This improved function, with left ventricular systolic pressure increasing from 103±4 mm Hg to 137±7 mm Hg (P<0.05). Eliminating elevations in preload after global ischemia-induced stunning also prevented TnI degradation.Conclusions—Calpain-mediated TnI proteolysis can be dissociated from stunning and arises from elevations in preload rather than ischemia. This raises the possibility that ongoing preload-induced TnI degradation could impair myocardial function long-term.