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Endolysosomal Ca2 + signaling in cardiovascular health and disease
International Review of Cell and Molecular Biology ( IF 6.420 ) Pub Date : 2021-05-03 , DOI: 10.1016/bs.ircmb.2021.03.001
Sharon Negri 1 , Pawan Faris 1 , Francesco Moccia 1
Affiliation  

An increase in intracellular Ca2 + concentration ([Ca2 +]i) regulates a plethora of functions in the cardiovascular (CV) system, including contraction in cardiomyocytes and vascular smooth muscle cells (VSMCs), and angiogenesis in vascular endothelial cells and endothelial colony forming cells. The sarco/endoplasmic reticulum (SR/ER) represents the largest endogenous Ca2 + store, which releases Ca2 + through ryanodine receptors (RyRs) and/or inositol-1,4,5-trisphosphate receptors (InsP3Rs) upon extracellular stimulation. The acidic vesicles of the endolysosomal (EL) compartment represent an additional endogenous Ca2 + store, which is targeted by several second messengers, including nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], and may release intraluminal Ca2 + through multiple Ca2 + permeable channels, including two-pore channels 1 and 2 (TPC1–2) and Transient Receptor Potential Mucolipin 1 (TRPML1). Herein, we discuss the emerging, pathophysiological role of EL Ca2 + signaling in the CV system. We describe the role of cardiac TPCs in β-adrenoceptor stimulation, arrhythmia, hypertrophy, and ischemia-reperfusion injury. We then illustrate the role of EL Ca2 + signaling in VSMCs, where TPCs promote vasoconstriction and contribute to pulmonary artery hypertension and atherosclerosis, whereas TRPML1 sustains vasodilation and is also involved in atherosclerosis. Subsequently, we describe the mechanisms whereby endothelial TPCs promote vasodilation, contribute to neurovascular coupling in the brain and stimulate angiogenesis and vasculogenesis. Finally, we discuss about the possibility to target TPCs, which are likely to mediate CV cell infection by the Severe Acute Respiratory Disease-Coronavirus-2, with Food and Drug Administration-approved drugs to alleviate the detrimental effects of Coronavirus Disease-19 on the CV system.



中文翻译:

心血管健康和疾病中的内溶酶体 Ca2 + 信号传导

细胞内 Ca 2  +浓度 ([Ca 2  + ] i ) 的增加调节心血管 (CV) 系统中的多种功能,包括心肌细胞和血管平滑肌细胞 (VSMC) 的收缩,以及血管内皮细胞和内皮细胞的血管生成集落形成细胞。肌/内质网 (SR/ER) 代表最大的内源性 Ca 2  +储存,其通过兰尼碱受体 (RyRs) 和/或肌醇-1,4,5-磷酸受体 (InsP 3 Rs)释放 Ca 2  +刺激。内溶酶体 (EL) 隔室的酸性囊泡代表额外的内源性 Ca 2 +存储,它是由几个第二信使,包括烟酸腺嘌呤二核苷酸磷酸(NAADP)和磷脂酰肌醇3,5-二磷酸[PI(3,5)p靶向2 ],并可能释放管腔内的Ca 2  +通过多个CA 2  +通透性通道,包括双孔通道 1 和 2 (TPC1-2) 和瞬态受体电位粘蛋白 1 (TRPML1)。在此,我们讨论了 EL Ca 2  +信号在 CV 系统中的新兴病理生理作用。我们描述了心脏 TPC 在 β-肾上腺素能受体刺激、心律失常、肥大和缺血再灌注损伤中的作用。然后我们说明EL Ca 2 +的作用 VSMC 中的信号传导,其中 TPC 促进血管收缩并导致肺动脉高压和动脉粥样硬化,而 TRPML1 维持血管舒张并参与动脉粥样硬化。随后,我们描述了内皮 TPC 促进血管舒张、促进大脑神经血管耦合以及刺激血管生成和血管生成的机制。最后,我们讨论了靶向 TPC 的可能性,这些 TPC 可能介导严重急性呼吸道疾病 - 冠状病毒 2 引起的 CV 细胞感染,以及食品和药物管理局批准的药物,以减轻冠状病毒疾病 19 对冠状病毒的不利影响简历系统。

更新日期:2021-05-03
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