Essential role for smooth muscle cell stromal interaction molecule-1 in myocardial infarction.
Essential role for smooth muscle cell stromal interaction molecule-1 in myocardial infarction.
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DOI：
10.1097/hjh.0000000000001518
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发表时间：
2018-03
影响因子：
4.9
通讯作者：
Matrougui K
中科院分区：
文献类型：
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作者：
Mali V;Haddox S;Belmadani S;Matrougui K
基质相互作用分子-1 （STIM1）在不同细胞类型的钙信号传导中起协调作用。心肌细胞中STIM1表达的增加或缺失会引起心脏并发症。此外，内皮细胞中STIM1的缺失会导致血管内皮功能障碍。然而，当小鼠注入血管紧张素- ii时，SMC中STIM1的破坏对内皮功能没有影响，但对血管功能有保护作用。然而，SMC-STIM1在急性缺血再灌注（I/R）损伤和永久性冠状动脉闭塞（PCO）引起的急慢性心肌梗死中的作用尚不清楚。生成Stim1fl/fl并交叉到SM22α-Cre+背景中。SM22α-Cre+导致成人SMC中STIM1固定基因的缺失（Stim1SMC−/−）。对照组和Stim1SMC - / -小鼠均遭受急性I/R损伤。然后采集心脏并与三苯基四氮唑氯孵育以确定梗死面积。在I/R对照小鼠中，心脏发生与STIM1表达增加相关的显著梗死。有趣的是，Stim1SMC - / -小鼠的梗死面积显著减小。Stim1SMC - / -小鼠对I/R损伤的保护作用涉及调节内质网（ER）应激、细胞凋亡、氧化应激、Akt和MAP-Kinase （ERK1/2和p38）信号传导以及炎症。此外，在另一种PCO诱导的慢性心肌梗死模型中，SMC-STIM1破坏可显著减少心肌梗死面积，改善心功能。我们的研究结果提供了新的证据，表明SMC-STIM1破坏是一种通过减少内质网应激、氧化应激、map -激酶、细胞凋亡和炎症来保护心脏免受心肌梗死的新机制。
Stromal Interacting Molecule-1 (STIM1) plays a role in co-ordinating calcium signaling in different cell types. The increase or deletion of STIM1 expression in cardiomyocyte causes cardiac complication. Moreover, the deletion of STIM1 in endothelial cell causes vascular endothelial dysfunction. However, the disruption of STIM1 in SMC has no effect on endothelial function but protects vascular function when mice are infused with angiotensin-II. Nevertheless, the role of SMC-STIM1 in acute and chronic myocardial infarction induced by acute ischemia-reperfusion (I/R) injury and permanent coronary artery occlusion (PCO) is unknown. Stim1fl/fl were generated and crossed into the SM22α-Cre+ backgrounds. SM22α-Cre+ causes deletion of STIM1 floxed genes in adult SMC (Stim1SMC−/−). Control and Stim1SMC−/− mice were subjected to acute I/R injury. Hearts were then harvested and incubated with triphenyl-tetrazolium chloride to determine the infarct size. In control mice subjected to I/R, the heart developed a significant infarct associated with an increase in STIM1 expression. Interestingly, the infarct size was substantially reduced in Stim1SMC−/− mice. The protection in Stim1SMC−/− mice against I/R injury involves the modulation of endoplasmic reticulum (ER) stress, apoptosis, oxidative stress, Akt and MAP-Kinase (ERK1/2 and p38) signaling, and inflammation. Furthermore, in another model of chronic myocardial infarction induced by PCO, SMC-STIM1 disruption significantly reduced myocardial infarct size and improved cardiac function. Our results provide new evidence that SMC-STIM1 disruption is a novel mechanism that protects the heart from myocardial infarction through reduction of ER stress, oxidative stress, MAP-Kinase, apoptosis, and inflammation.