PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia.
PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia.
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DOI：
10.1038/s41598-021-81170-2
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发表时间：
2021-01-15
影响因子：
4.6
通讯作者：
Oceandy D
中科院分区：
文献类型：
--
作者：
Stafford N;Zi M;Baudoin F;Mohamed TMA;Prehar S;De Giorgio D;Cartwright EJ;Latini R;Neyses L;Oceandy D
缺血性心脏病是世界上主要的死亡原因。近年来，急性心肌梗死（MI）的生存率有所提高;然而，由于梗死心肌的慢性重塑，导致心力衰竭（HF）的患病率增加，治疗选择仍然很差。我们以前已经表明，抑制质膜钙ATP酶（PMCA 4）的亚型4可以通过成纤维细胞介导的Wnt信号调节，防止压力超负荷期间的慢性重塑和HF发展。鉴于Wnt信号传导在梗死心脏重塑过程中也起着重要作用，本研究调查了PMCA 4的遗传和功能缺失对MI后心脏结局的影响。无论是基因缺失还是药物抑制PMCA 4都不会影响MI后心肌的慢性重塑。这是当PMCA 4被整体删除，或特别是从心肌细胞或成纤维细胞删除时的情况。然而，PMCA 4消融的心脏不太容易发生急性心肌梗死事件，这可能会提供轻微的生存益处。总体而言，这项研究表明，PMCA 4抑制不影响MI后的慢性结局。
Ischaemic heart disease is the world’s leading cause of mortality. Survival rates from acute myocardial infarction (MI) have improved in recent years; however, this has led to an increase in the prevalence of heart failure (HF) due to chronic remodelling of the infarcted myocardium, for which treatment options remain poor. We have previously shown that inhibition of isoform 4 of the plasma membrane calcium ATPase (PMCA4) prevents chronic remodelling and HF development during pressure overload, through fibroblast mediated Wnt signalling modulation. Given that Wnt signalling also plays a prominent role during remodelling of the infarcted heart, this study investigated the effect of genetic and functional loss of PMCA4 on cardiac outcomes following MI. Neither genetic deletion nor pharmacological inhibition of PMCA4 affected chronic remodelling of the post-MI myocardium. This was the case when PMCA4 was deleted globally, or specifically from cardiomyocytes or fibroblasts. PMCA4-ablated hearts were however less prone to acute arrhythmic events, which may offer a slight survival benefit. Overall, this study demonstrates that PMCA4 inhibition does not affect chronic outcomes following MI.
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影响因子：
2.1
作者：
Galli A;Lombardi F
通讯作者：
Lombardi F
英国心血管疾病流行病学的趋势。
DOI：
10.1136/heartjnl-2016-309573
发表时间：
2016-12-15
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Bhatnagar P;Wickramasinghe K;Wilkins E;Townsend N
通讯作者：
Townsend N
影响因子：
20.1
作者：
Gyöngyösi M;Wojakowski W;Lemarchand P;Lunde K;Tendera M;Bartunek J;Marban E;Assmus B;Henry TD;Traverse JH;Moyé LA;Sürder D;Corti R;Huikuri H;Miettinen J;Wöhrle J;Obradovic S;Roncalli J;Malliaras K;Pokushalov E;Romanov A;Kastrup J;Bergmann MW;Atsma DE;Diederichsen A;Edes I;Benedek I;Benedek T;Pejkov H;Nyolczas N;Pavo N;Bergler-Klein J;Pavo IJ;Sylven C;Berti S;Navarese EP;Maurer G;ACCRUE Investigators
通讯作者：
ACCRUE Investigators
DOI：
10.1073/pnas.0610024104
发表时间：
2007-01-30
影响因子：
11.1
作者：
Mirotsou, Maria;Zhang, Zhongyan;Dzau, Victor
通讯作者：
Dzau, Victor
DOI：
10.1073/pnas.0803437105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Alfaro, Maria P.;Pagni, Matthew;Young, Pampee P.
通讯作者：
Young, Pampee P.