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RCAN1 在心血管疾病中的作用:分子机制与潜在治疗靶点。

RCAN1 in cardiovascular diseases: molecular mechanisms and a potential therapeutic target.

机构信息

Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, Jining Medical University, Jianshe South Road No. 45, Rencheng District, Jining, 272013, Shandong, China.

Shandong Key Laboratory of Behavioral Medicine, School of Mental Health, Jining Medical University, Jianshe South Road No. 45, Rencheng District, Jining, 272013, Shandong, China.

出版信息

Mol Med. 2020 Dec 2;26(1):118. doi: 10.1186/s10020-020-00249-0.

Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Considerable efforts are needed to elucidate the underlying mechanisms for the prevention and treatment of CVDs. Regulator of calcineurin 1 (RCAN1) is involved in both development/maintenance of the cardiovascular system and the pathogenesis of CVDs. RCAN1 reduction protects against atherosclerosis by reducing the uptake of oxidized low-density lipoproteins, whereas RCAN1 has a protective effect on myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma/aortic rupture mainly mediated by maintaining mitochondrial function and inhibiting calcineurin and Rho kinase activity, respectively. In this review, the regulation and the function of RCAN1 are summarized. Moreover, the dysregulation of RCAN1 in CVDs is reviewed. In addition, the beneficial role of RCAN1 reduction in atherosclerosis and the protective role of RCAN1 in myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma /aortic rupture are discussed, as well as underlying mechanisms. Furthermore, the therapeutic potential and challenges of targeting RCAN1 for CVDs treatment are also discussed.

摘要

心血管疾病(CVDs)是全球范围内的主要死亡原因。需要付出相当大的努力来阐明 CVDs 的预防和治疗的潜在机制。钙调神经磷酸酶 1 调节因子(RCAN1)既参与心血管系统的发育/维持,也参与 CVDs 的发病机制。RCAN1 的减少通过减少氧化型低密度脂蛋白的摄取来保护动脉粥样硬化,而 RCAN1 对心肌缺血/再灌注损伤、心肌肥厚和壁内血肿/主动脉破裂具有保护作用,主要通过维持线粒体功能和抑制钙调神经磷酸酶和 Rho 激酶活性来实现。在这篇综述中,总结了 RCAN1 的调节和功能。此外,还综述了 RCAN1 在 CVDs 中的失调。此外,还讨论了 RCAN1 减少在动脉粥样硬化中的有益作用,以及 RCAN1 在心肌缺血/再灌注损伤、心肌肥厚和壁内血肿/主动脉破裂中的保护作用及其潜在机制。此外,还讨论了针对 RCAN1 治疗 CVDs 的治疗潜力和挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d16/7709393/c316c928f692/10020_2020_249_Fig1_HTML.jpg

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