Alterations to myofibrillar protein function in nonischemic regions of the heart early after myocardial infarction.

Alterations to myofibrillar protein function in nonischemic regions of the heart early after myocardial infarction.
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心肌梗塞后早期心脏非缺血区域肌原纤维蛋白功能的改变。

DOI:
10.1152/ajpheart.01314.2006
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发表时间:
2007
期刊:
American journal of physiology. Heart and circulatory physiology
影响因子:
--
通讯作者:
Guilford,WilliamH
Guilford,WilliamH
中科院分区:
--
文献类型:
--
作者:
Rao,VijayS;LaBonte,LauraR;Xu,Yaqin;Yang,Zequan;French,BrentA;Guilford,WilliamH

文献摘要

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Remote-zone left ventricular dysfunction (LVD) contributes to global reductions in contractile function after localized myocardial infarction (MI). However, the molecular mechanisms underlying this form of LVD are not clear. This study tested the hypothesis that myofibrillar protein function is directly affected in remote-zone LVD early after MI. Cardiac myosin and native thin filaments were purified from mouse myocardium taken from both the nonnecrotic zone adjacent to and the nonischemic zone remote from an infarct induced by 1 h of coronary occlusion followed by 24 h of reperfusion. Thin filament velocities were measured using the in vitro motility assay. Results showed that overall function was significantly reduced in samples from both the adjacent (43 ± 12% of control,n= 7) and remote (53 ± 8% of control,n= 13) zones when compared with control proteins (P< 0.05). Myosin from the remote zone propelled control thin filaments at reduced velocities similar to those measured above. In contrast, the Ca2+sensitivity of remote-zone thin filaments over control myosin was unchanged from control thin filaments (half-maximal at pCa 6.32 ± 0.08 and 6.27 ± 0.06, respectively) but showed a 20% increase in velocity at saturating Ca2+that parallels an increase in tropomyosin phosphorylation. Myosin dysfunction may be related to oxidation of cysteines in the myosin heavy chains or carbonylation of myosin binding protein-C. We hypothesize that phosphorylation of tropomyosin may serve a compensatory role, augmenting contraction during periods of oxidative stress when myosin function is compromised.