Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.
Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.
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DOI：
10.1016/j.yjmcc.2011.09.011
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发表时间：
2012-01
影响因子：
5
通讯作者：
Sadayappan S
中科院分区：
文献类型：
--
作者：
Govindan S;McElligott A;Muthusamy S;Nair N;Barefield D;Martin JL;Gongora E;Greis KD;Luther PK;Winegrad S;Henderson KK;Sadayappan S
心肌肌球蛋白结合蛋白-C (cMyBP-C) 是一种粗丝组装蛋白，可稳定肌节结构并调节心脏功能；然而，心肌梗塞 (MI) 后 cMyBP-C 降解的情况尚不清楚。我们假设 cMyBP-C 对蛋白水解敏感，并且在大鼠和人类的心肌梗死后血流中特别增加。在这种情况下，降解的 cMyBP-C 水平升高可以用作确认 MI 的诊断工具。为了检验这一假设，我们首先确定 cMyBP-C 去磷酸化与这种肌丝蛋白的降解增加直接相关，从而导致其在体外释放。在体外使用新生大鼠心室心肌细胞，我们能够将缺氧应激的诱导与 cMyBP-C 去磷酸化、降解和 N' 片段的特异性释放增加相关联。接下来，为了确定 MI 后 cMyBP-C 的蛋白水解模式，结扎成年雄性大鼠的左冠状动脉前降支。通过总 cMyBP-C 的减少和梗塞组织中降解产物的存在证实了 cMyBP-C 的降解。与非缺血区域和假对照心脏相比，MI 心脏缺血区域的 cMyBP-C 磷酸化水平大大降低。通过夹心 ELISA 和免疫沉淀分析，对这些大鼠以及人类的 MI 后血浆样本进行 cMyBP-C 及其片段分析。结果显示，所有 MI 后样本血浆中的 cMyBP-C 水平显着升高。总体而言，这项研究表明 cMyBP-C 是一种易于释放的肌丝蛋白，在心肌梗死后会被去磷酸化、降解并释放到循环中。血液中 cMyBP-C 水平升高提供了一种有前景的新型生物标志物，能够准确判断心肌梗死，从而有助于进一步评估缺血性心脏病。
Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N′-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease.
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影响因子：
15.9
作者：
McConnell, BK;Jones, KA;Seidman, JG
通讯作者：
Seidman, JG
影响因子：
158.5
作者：
Keller, Till;Zeller, Tanja;Blankenberg, Stefan
通讯作者：
Blankenberg, Stefan
影响因子：
37.8
作者：
Decker, RS;Decker, ML;Winegrad, S
通讯作者：
Winegrad, S
DOI：
10.1085/jgp.200308941
发表时间：
2003-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Kulikovskaya I;McClellan G;Flavigny J;Carrier L;Winegrad S
通讯作者：
Winegrad S
影响因子：
9.7
作者：
Henderson, Kyle K.;Danzi, Sara;Samarel, Allen M.
通讯作者：
Samarel, Allen M.