AstragalosideⅣ against cardiac fibrosis by inhibiting TRPM7 channel

Lu, Jun Q.; Wang, Quanyi; Zhou, Yang; Lu, Xiaochun; Liu, Yonghui; Wu, Yan; Guo, Qiaoling; Ma, Yun-Tian; Tang, Yiqun

doi:10.1016/j.phymed.2017.04.002

Cited by 32 publications

(34 citation statements)

References 34 publications

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“…Using also hypoxia as stimulus, it was proposed that the increased TRPM7 expression and activity in rat CFs during hypoxia is blocked by astragaloside-IV (most active component of Chinese sp. Astragalus), and that its inhibition by siRNA prevents fibrotic features in NIH-3T3 mouse fibroblasts [101]. Additionally, in rat CFs H 2 O 2 and AngII also are able to provoke a sustained increase in the intracellular Ca 2+ and elevated expression of fibrogenic growth factors (e.g., α-SMA, TGF-β1) that were either blunted or reduced in fibroblasts in which TRPM7 was silenced via shRNA [102].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels

Londoño

Marx

Kraft

et al. 2020

Cells

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TRPC proteins form cation conducting channels regulated by different stimuli and are regulators of the cellular calcium homeostasis. TRPC are expressed in cardiac cells including cardiac fibroblasts (CFs) and have been implicated in the development of pathological cardiac remodeling including fibrosis. Using Ca2+ imaging and several compound TRPC knockout mouse lines we analyzed the involvement of TRPC proteins for the angiotensin II (AngII)-induced changes in Ca2+ homeostasis in CFs isolated from adult mice. Using qPCR we detected transcripts of all Trpc genes in CFs; Trpc1, Trpc3 and Trpc4 being the most abundant ones. We show that the AngII-induced Ca2+ entry but also Ca2+ release from intracellular stores are critically dependent on the density of CFs in culture and are inversely correlated with the expression of the myofibroblast marker α-smooth muscle actin. Our Ca2+ measurements depict that the AngII- and thrombin-induced Ca2+ transients, and the AngII-induced Ca2+ entry and Ca2+ release are not affected in CFs isolated from mice lacking all seven TRPC proteins (TRPC-hepta KO) compared to control cells. However, pre-incubation with GSK7975A (10 µM), which sufficiently inhibits CRAC channels in other cells, abolished AngII-induced Ca2+ entry. Consequently, we conclude the dispensability of the TRPC channels for the acute neurohumoral Ca2+ signaling evoked by AngII in isolated CFs and suggest the contribution of members of the Orai channel family as molecular constituents responsible for this pathophysiologically important Ca2+ entry pathway.

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Section: Discussionmentioning

confidence: 99%

Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels

Londoño

Marx

Kraft

et al. 2020

Cells

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“…Moreover, in rats with sick sinus syndrome, TRPM7 regulated angiotensin II-induced cardiac fibroblasts proliferation and collagen synthesis of sinoatrial node, involving Smad signaling pathway (Zhong et al., 2018b). Recently, a role of TRPM7 was reported in miRNA-135a inhibition of isoproterenol-induced cardiac fibrosis (Wu et al., 2018) and in fibrosis evoked by H 2 O 2 and hypoxia (Guo et al., 2014; Lu et al., 2017). Therefore, TRPM7 stand out as an interesting possible target to attenuate pathological cardiac fibrosis.…”

Section: Role Of Trp Channels In the Adverse Cardiac Remodelingmentioning

confidence: 99%

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

et al. 2019

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Calcium is an important second messenger required not only for the excitation-contraction coupling of the heart but also critical for the activation of cell signaling pathways involved in the adverse cardiac remodeling and consequently for the heart failure. Sustained neurohumoral activation, pressure-overload, or myocardial injury can cause pathologic hypertrophic growth of the heart followed by interstitial fibrosis. The consequent heart’s structural and molecular adaptation might elevate the risk of developing heart failure and malignant arrhythmia. Compelling evidences have demonstrated that Ca 2+ entry through TRP channels might play pivotal roles in cardiac function and pathology. TRP proteins are classified into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin), which are activated by numerous physical and/or chemical stimuli. TRP channels participate to the handling of the intracellular Ca 2+ concentration in cardiac myocytes and are mediators of different cardiovascular alterations. This review provides an overview of the current knowledge of TRP proteins implication in the pathologic process of some frequent cardiac diseases associated with the adverse cardiac remodeling such as cardiac hypertrophy, fibrosis, and conduction alteration.

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“…In vivo and in vitro studies have shown that AS-IV can reduce the expression of TRPM7 and its mRNA, inhibit the activation of the TGF-β/Smads pathway, and inhibit myocardial fibrosis. 69 , 70 The mechanism by which AS-IV inhibits ISO-induced myocardial fibrosis may be related to ROS-mediated responses. It has been found that both increased ROS content and upregulated cardiotrophin 1 (CT1) expression, both of which were inhibited after the addition of astragaloside, which inhibited cardiac fibroblast proliferation and collagen production.…”

Section: Introductionmentioning

confidence: 99%

<p>Astragaloside IV: An Effective Drug for the Treatment of Cardiovascular Diseases</p>

Tan¹,

Chen²,

Li³

2020

DDDT

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Cardiovascular disease (CVD), the number one cause of death worldwide, has always been the focus of clinical and scientific research. Due to the high number of deaths each year, it is essential to find alternative therapies that are safe and effective with minimal side effects. Traditional Chinese medicine (TCM) has a long history of significant impact on the treatment of CVDs. The mode of action of natural active ingredients of drugs and the development of new drugs are currently hot topics in research on TCM. Astragalus membranaceus is a commonly used Chinese medicinal herb. Previous studies have shown that Astragalus membranaceus has anti-tumor properties and can regulate metabolism, enhance immunity, and strengthen the heart. Astragaloside IV (AS-IV) is the active ingredient of Astragalus membranaceus , which has a prominent role in cardiovascular diseases. AS-IV can protect against ischemic and hypoxic myocardial cell injury, inhibit myocardial hypertrophy and myocardial fibrosis, enhance myocardial contractility, improve diastolic dysfunction, alleviate vascular endothelial dysfunction, and promote angiogenesis. It can also regulate blood glucose and blood lipid levels and reduce the risk of cardiovascular diseases. In this paper, the mechanism of AS-IV intervention in cardiovascular diseases in recent years is reviewed in order to provide a reference for future research and new drug development.

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AstragalosideⅣ against cardiac fibrosis by inhibiting TRPM7 channel

Cited by 32 publications

References 34 publications

Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels

Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

<p>Astragaloside IV: An Effective Drug for the Treatment of Cardiovascular Diseases</p>

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