钙库操纵性钙内流在心血管和骨骼肌疾病及血管生成中的病理生理意义。

Pathophysiological Significance of Store-Operated Calcium Entry in Cardiovascular and Skeletal Muscle Disorders and Angiogenesis.

机构信息

Department of Medical Physiology and Biophysics, University of Seville, Sevilla, Spain.

Institute of Biomedicine of Seville (IBiS), University Hospital of Virgen del Rocío/CSIC/University of Seville, Sevilla, Spain.

出版信息

Adv Exp Med Biol. 2020;1131:489-504. doi: 10.1007/978-3-030-12457-1_19.

DOI:10.1007/978-3-030-12457-1_19

PMID:31646522

Abstract

Store-Operated Ca Entry (SOCE) is an important Ca influx pathway expressed by several excitable and non-excitable cell types. SOCE is recognized as relevant signaling pathway not only for physiological process, but also for its involvement in different pathologies. In fact, independent studies demonstrated the implication of essential protein regulating SOCE, such as STIM, Orai and TRPCs, in different pathogenesis and cell disorders, including cardiovascular disease, muscular dystrophies and angiogenesis. Compelling evidence showed that dysregulation in the function and/or expression of isoforms of STIM, Orai or TRPC play pivotal roles in cardiac hypertrophy and heart failure, vascular remodeling and hypertension, skeletal myopathies, and angiogenesis. In this chapter, we summarized the current knowledge concerning the mechanisms underlying abnormal SOCE and its involvement in some diseases, as well as, we discussed the significance of STIM, Orai and TRPC isoforms as possible therapeutic targets for the treatment of angiogenesis, cardiovascular and skeletal muscle diseases.

摘要

钙库操纵性钙内流（SOCE）是几种可兴奋和非兴奋细胞类型表达的重要钙内流途径。SOCE 不仅被认为是与生理过程相关的信号通路，也与多种病理过程相关。事实上，独立的研究表明，调节 SOCE 的重要蛋白，如 STIM、Orai 和 TRPCs，参与了不同的发病机制和细胞紊乱，包括心血管疾病、肌肉萎缩症和血管生成。强有力的证据表明，STIM、Orai 或 TRPC 异构体的功能和/或表达失调在心脏肥大和心力衰竭、血管重塑和高血压、骨骼肌疾病和血管生成中起着关键作用。在这一章中，我们总结了关于异常 SOCE 的发生机制及其在某些疾病中的作用的最新知识，并讨论了 STIM、Orai 和 TRPC 异构体作为治疗血管生成、心血管和骨骼肌疾病的潜在治疗靶点的意义。