A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.
A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.
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DOI：
10.1152/ajpheart.00899.2015
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发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Ferenczi MA
中科院分区：
文献类型：
--
作者：
Toepfer CN;Sikkel MB;Caorsi V;Vydyanath A;Torre I;Copeland O;Lyon AR;Marston SB;Luther PK;Macleod KT;West TG;Ferenczi MA
大鼠慢性心肌梗死后的代偿性心肌梗死（CMI）的特征是在生理性缩短过程中，伴随着经典的肥大，在小梁中产生的力和功率增加。肌节收缩增益受到涉及肌球蛋白结合蛋白C（MyBP-C）减少和调节轻链（RLC）磷酸化升高的机制的影响。慢性心肌梗死（CMI）后的心肌重塑分为两个阶段：肥厚性“代偿”和充血性“失代偿”。在这些临床阶段，未梗死心肌产生力、速度和功率的能力尚不清楚，尽管这些区域的适应可能会推动代偿的进展。我们假设，增强跨桥水平的收缩性的基础机械补偿，并在一定程度上控制肌球蛋白调节蛋白的磷酸化状态的变化。采用结扎大鼠冠状动脉左前降支的方法建立心肌梗死模型。然后，我们测量了机械性能的透性心室小梁采取远离梗死区和测定肌球蛋白调节蛋白磷酸化在每个人的小梁。在完全激活过程中，与非梗死对照组相比，代偿心肌产生的功率是其两倍，等长收缩力增加31%。次最大激活期间的等距力提高>2.4倍，而功率大2倍。电子和共聚焦显微镜表明，这些机械变化不是收缩蛋白密度增加的结果，因此不是组织肥大的影响。因此，肌节水平的收缩适应是增强小梁力学和整体心脏代偿反应的关键决定因素。心肌梗死后，肌球蛋白调节轻链（RLC）磷酸化水平升高并保持升高，而肌球蛋白结合蛋白-C（MyBP-C）磷酸化水平最初受到抑制，但随着心脏失代偿而升高。这些敏感性CMI是根据磷酸化依赖的调控作用，RLC和MyBP-C在横桥功能和代偿性适应的力量和权力，我们观察到在CMI后小梁。
Compensation postchronic myocardial infarction (CMI) in rats is characterized in trabeculae as increased force and power production during physiological shortening, which occurs alongside classical hypertrophy. Sarcomeric contractile gain is influenced by mechanisms involving reduced myosin binding protein C (MyBP-C) and raised regulatory light chain (RLC) phosphorylation. Myocardial remodeling in response to chronic myocardial infarction (CMI) progresses through two phases, hypertrophic “compensation” and congestive “decompensation.” Nothing is known about the ability of uninfarcted myocardium to produce force, velocity, and power during these clinical phases, even though adaptation in these regions likely drives progression of compensation. We hypothesized that enhanced cross-bridge-level contractility underlies mechanical compensation and is controlled in part by changes in the phosphorylation states of myosin regulatory proteins. We induced CMI in rats by left anterior descending coronary artery ligation. We then measured mechanical performance in permeabilized ventricular trabecula taken distant from the infarct zone and assayed myosin regulatory protein phosphorylation in each individual trabecula. During full activation, the compensated myocardium produced twice as much power and 31% greater isometric force compared with noninfarcted controls. Isometric force during submaximal activations was raised >2.4-fold, while power was 2-fold greater. Electron and confocal microscopy demonstrated that these mechanical changes were not a result of increased density of contractile protein and therefore not an effect of tissue hypertrophy. Hence, sarcomere-level contractile adaptations are key determinants of enhanced trabecular mechanics and of the overall cardiac compensatory response. Phosphorylation of myosin regulatory light chain (RLC) increased and remained elevated post-MI, while phosphorylation of myosin binding protein-C (MyBP-C) was initially depressed but then increased as the hearts became decompensated. These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae.
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影响因子：
20.1
作者：
de Waard, Monique C.;van der Velden, Jolanda;Duncker, Dirk J.
通讯作者：
Duncker, Dirk J.
DOI：
10.1098/rspb.1938.0050
发表时间：
1938-10-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Hill, AV
通讯作者：
Hill, AV
影响因子：
4.3
作者：
Avner, Benjamin S.;Shioura, Krystyna M.;Scruggs, Sarah B.;Grachoff, Milana;Geenen, David L.;Helseth, Donald L., Jr.;Farjah, Mariam;Goldspink, Paul H.;Solaro, R. John
通讯作者：
Solaro, R. John
影响因子：
2.9
作者：
Coulton, Arthur T.;Stelzer, Julian E.
通讯作者：
Stelzer, Julian E.
影响因子：
5
作者：
Gupta, Manish K.;Gulick, James;Robbins, Jeffrey
通讯作者：
Robbins, Jeffrey