Schumacher David, Curaj Adelina, Staudt Mareike, Cordes Franziska, Dumitraşcu Andreea R, Rolles Benjamin, Beckers Christian, Soppert Josefin, Rusu Mihaela, Simsekyilmaz Sakine, Kneizeh Kinan, Ramachandra Chrishan J A, Hausenloy Derek J, Liehn Elisa A
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, 52074 Aachen, Germany.
Int J Mol Sci. 2021 Apr 22;22(9):4401. doi: 10.3390/ijms22094401.
Phosphatidylserines are known to sustain skeletal muscle activity during intense activity or hypoxic conditions, as well as preserve neurocognitive function in older patients. Our previous studies pointed out a potential cardioprotective role of phosphatidylserine in heart ischemia. Therefore, we investigated the effects of phosphatidylserine oral supplementation in a mouse model of acute myocardial infarction (AMI). We found out that phosphatidylserine increases, significantly, the cardiomyocyte survival by 50% in an acute model of myocardial ischemia-reperfusion. Similar, phosphatidylserine reduced significantly the infarcted size by 30% and improved heart function by 25% in a chronic model of AMI. The main responsible mechanism seems to be up-regulation of protein kinase C epsilon (PKC-ε), the main player of cardio-protection during pre-conditioning. Interestingly, if the phosphatidylserine supplementation is started before induction of AMI, but not after, it selectively inhibits neutrophil's activation, such as Interleukin 1 beta (IL-1β) expression, without affecting the healing and fibrosis. Thus, phosphatidylserine supplementation may represent a simple way to activate a pre-conditioning mechanism and may be a promising novel strategy to reduce infarct size following AMI and to prevent myocardial injury during myocardial infarction or cardiac surgery. Due to the minimal adverse effects, further investigation in large animals or in human are soon possible to establish the exact role of phosphatidylserine in cardiac diseases.
已知磷脂酰丝氨酸可在剧烈活动或缺氧条件下维持骨骼肌活动，还能保护老年患者的神经认知功能。我们之前的研究指出磷脂酰丝氨酸在心脏缺血中可能具有心脏保护作用。因此，我们在急性心肌梗死（AMI）小鼠模型中研究了口服补充磷脂酰丝氨酸的效果。我们发现，在急性心肌缺血-再灌注模型中，磷脂酰丝氨酸可使心肌细胞存活率显著提高50%。同样，在AMI慢性模型中，磷脂酰丝氨酸可使梗死面积显著减少30%，并使心脏功能改善25%。主要的作用机制似乎是上调蛋白激酶Cε（PKC-ε），它是预处理期间心脏保护的主要参与者。有趣的是，如果在诱导AMI之前而非之后开始补充磷脂酰丝氨酸，它会选择性抑制中性粒细胞的激活，如白细胞介素1β（IL-1β）的表达，而不影响愈合和纤维化。因此，补充磷脂酰丝氨酸可能是激活预处理机制的一种简单方法，可能是减少AMI后梗死面积以及预防心肌梗死或心脏手术期间心肌损伤的一种有前景的新策略。由于不良反应极小，很快就有可能在大型动物或人类中进行进一步研究，以确定磷脂酰丝氨酸在心脏疾病中的确切作用。
