Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

Zheng, Chang‐Bo; Gao, Wen‐Cong; Xie, Mingxu; Li, Zhichao; Ma, Xin; Song, Wencong; Luo, Dan; Huang, Yongxiang; Yang, Jichen; Zhang, Peng; Huang, Yu; Ye, Weimin; Yao, Xiaoqiang

doi:10.3389/fphar.2021.622774

Cited by 18 publications

(17 citation statements)

References 39 publications

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“…In contrast, with these studies, other studies have suggested that STIM1/Orai1 stimulates autophagy [64][65][66]. In cardiomyocyte, the silencing of Orai1 could markedly attenuate the Ang II-induced LC3-II accumulation and inhibited autophagy both in vitro and in vivo [64]. It seems that the autophagy-related role of Orai1 and SOCE can be either stimulating or inhibiting depending on the cell type or the stimulation it receives.…”

Section: Transient Receptor Potential Canonical and Orai1 Channelsmentioning

confidence: 73%

“…Another group showed that the knockdown of Orai1 enhances the 5-fluorouracil (5-FU)-induced inhibition of the phosphoinositide 3-kinase-AKT-mTOR pathway and potentiated 5-FU activated autophagic cell death in hepatocarcinoma cells [63]. In contrast, with these studies, other studies have suggested that STIM1/Orai1 stimulates autophagy [64][65][66]. In cardiomyocyte, the silencing of Orai1 could markedly attenuate the Ang II-induced LC3-II accumulation and inhibited autophagy both in vitro and in vivo [64].…”

Section: Transient Receptor Potential Canonical and Orai1 Channelsmentioning

confidence: 97%

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Calcium Signaling Regulates Autophagy and Apoptosis

Sukumaran

Conceicao

Sun

et al. 2021

Cells

133

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Calcium (Ca2+) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca2+ has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca2+ also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca2+ signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.

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Section: Transient Receptor Potential Canonical and Orai1 Channelsmentioning

confidence: 73%

Section: Transient Receptor Potential Canonical and Orai1 Channelsmentioning

confidence: 97%

Calcium Signaling Regulates Autophagy and Apoptosis

Sukumaran

Conceicao

Sun

et al. 2021

Cells

133

View full text Add to dashboard Cite

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“…Various preclinical studies documented that AngII mediates myocardial structural protein alterations, such as the overexpression of the β isoform of the myosin heavy chain (MHC) and the skeleton actin protein as well as cardiac fibrosis through the JMJD1C/TIMP 1 [44] and FOXF1/TGFβ 1/SMAD3 [45] signaling pathways as well as the involvement of the CD38/SIRT3 (Sirtuin)-FOXO3, Ca 2+ -calcineurin-NFAT (nuclear factor of activated T cells) [46], and TNFα/NFkB/CD44 signaling pathways [47]. In addition, AngII induces the upregulation of autophagy to mediate its cardiac pathogenesis through the activation of SOCE (store operated Ca 2+ entry)/Orai1 (a pore forming subunit for calcium permeation)/STIM1(Ca 2+ sensor) [48] and the inhibition of mammalian sterile 20-like kinase 1 (Mst1), a mediator of the Hippo signaling pathway [49]. In an experimental animal model of heart failure, it was documented that AngII decreased the levels of circulating IGF1 and elevated IGF1 and the expression of its specific receptor in the cardiac muscles [50].…”

Section: Angiotensin Ii-induced Cardiac Dysfunction Mimics Cardiac Ca...mentioning

confidence: 99%

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients

Saha

Singh

Roy

et al. 2022

Cells

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Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are autophagy activation by the cytokine-NFkB, TGF β-SMAD3, and angiotensin II-SOCE-STIM-Ca2+ pathways. A lack of diagnostic markers and standard treatment protocols hinder the early diagnosis of cardiac dysfunction and the initiation of preventive measures. However, some novel therapeutic strategies, including the use of Withaferin A, have shown promising results in experimental models, but Withaferin A’s effectiveness in human remains to be verified. The combined efforts of cardiologists and oncologists would help to identify cost effective and feasible solutions to restore cardiac function and to increase the survival potential of cancer patients.

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“…Angiotensin II (Ang II), a bioactive octa-peptide, is the representative hormone in RAS. Accumulating evidence shows that Ang II contributes to pathological cardiac hypertrophy and the resultant heart failure, indirectly via increased blood pressure and/or directly acting on cardiomyocytes [ 3–5 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-410-3p facilitates Angiotensin II–induced cardiac hypertrophy by targeting Smad7

Jia

Liang

et al. 2021

Bioengineered

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MicroRNAs (miRNAs) have emerged as important regulators in the development of cardiovascular diseases. miR-410-3p was shown to play a protective or detrimental role in the progression in cardiovascular events. However, the exact role and the underlying mechanism of miR-410-3p in cardiac hypertrophy have not been documented. The current work was aimed to determine the role and underlying mechanism of miR-410-3p on Angiotensin II (Ang II) induced cardiac hypertrophy. FITC-phalloidin staining was used for determination of cardiomyocyte surface area. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to identify mRNA expression level of hypertrophic markers. Smad7 protein expression level was analyzed using Western blot. Dual-luciferase reporter assay was used to examine the regulatory function of miR-410-3p on Smad7. MiR-410-3p was found significantly up-regulated in Ang II–induced cardiac hypertrophy. MiR-410-3p inhibitor remarkably alleviated cardiomyocyte hypertrophic changes. Dual-luciferase reporter assay result indicated that miR-410-3p directly targeted Smad7 and miR-410-3p inhibitor effectively prevented Ang II triggered down-regulation of Smad7. Moreover, Smad7 overexpression significantly reversed the pro-hypertrophic effect of miR-410-3p. In summary, our findings revealed that miR-410-3p mediated Ang II–induced cardiac hypertrophy via targeting inhibition of Smad7.

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Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

Cited by 18 publications

References 39 publications

Calcium Signaling Regulates Autophagy and Apoptosis

Calcium Signaling Regulates Autophagy and Apoptosis

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients

MiR-410-3p facilitates Angiotensin II–induced cardiac hypertrophy by targeting Smad7

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