Transgenic overexpression of transient receptor potential vanilloid subtype 1 attenuates isoproterenol-induced myocardial fibrosis in mice

Wang, Qiang; Zhang, Yunrong; De, Li; Zhang, Yan; Tang, Bing; Li, Gang; Yang, Yongjian; Yang, Dachun

doi:10.3892/ijmm.2016.2648

Cited by 17 publications

(22 citation statements)

References 42 publications

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“…For several TRP proteins different mechanisms for their involvement in fibroblast function and fibrosis development have been proposed. In CFs from TRPV1 over-expressing mice the sustained Ca 2+ rise provoked by capsaicin is enhanced; additionally, in those mice the Isoproterenol-induced cardiac fibrosis and cardiac hypertrophy in vivo are reduced [91]. In vitro, the AngII-induced proliferation of CFs is reduced by capsaicin in cells from WT but not from TRPV1-deficient mice [92].…”

Section: Discussionmentioning

confidence: 96%

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: 96%

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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“…It has also been shown that capsaicin reduces fibroblast proliferation induced by AngII in vitro [173]. Moreover, overexpression of TRPV1 in transgenic mice attenuates isoproterenol-induced myocardial fibrosis [174], and the activation of TRPV1 has also been shown to be protective in a myocardial injury model [175][176][177]. On the contrary, other studies demonstrate that administration of a TRPV1 antagonist BCTC (4-(3-Chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide) prevents the loss of heart function, and protects the heart from fibrosis in a pressure-overload mouse model [208].…”

Section: Trpv1 and Cardiac Fibrosismentioning

confidence: 98%

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Feng

Armillei

et al. 2019

JCDD

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Cardiac fibrosis is the excessive deposition of extracellular matrix proteins by cardiac fibroblasts and myofibroblasts, and is a hallmark feature of most heart diseases, including arrhythmia, hypertrophy, and heart failure. This maladaptive process occurs in response to a variety of stimuli, including myocardial injury, inflammation, and mechanical overload. There are multiple signaling pathways and various cell types that influence the fibrogenesis cascade. Fibroblasts and myofibroblasts are central effectors. Although it is clear that Ca2+ signaling plays a vital role in this pathological process, what contributes to Ca2+ signaling in fibroblasts and myofibroblasts is still not wholly understood, chiefly because of the large and diverse number of receptors, transporters, and ion channels that influence intracellular Ca2+ signaling. Intracellular Ca2+ signals are generated by Ca2+ release from intracellular Ca2+ stores and by Ca2+ entry through a multitude of Ca2+-permeable ion channels in the plasma membrane. Over the past decade, the transient receptor potential (TRP) channels have emerged as one of the most important families of ion channels mediating Ca2+ signaling in cardiac fibroblasts. TRP channels are a superfamily of non-voltage-gated, Ca2+-permeable non-selective cation channels. Their ability to respond to various stimulating cues makes TRP channels effective sensors of the many different pathophysiological events that stimulate cardiac fibrogenesis. This review focuses on the mechanisms of Ca2+ signaling in fibroblast differentiation and fibrosis-associated heart diseases and will highlight recent advances in the understanding of the roles that TRP and other Ca2+-permeable channels play in cardiac fibrosis.

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“…On the other side, genetic models provide detailed understanding of the role of various targets in understanding disease pathology. Various genetic model such as low and high level transgenic expression of β2‐adrenergic receptors related models, phosphoinositide 3‐kinase γ‐deficient mice, and overexpression of transient receptor potential vanilloid subtype 1 channel, related models have been used to study the pathophysiology of heart failure (Dorn, Tepe, Lorenz, Koch, & Liggett, ; Hasenfuss, ; Oudit et al, ; Wang, Zhang, et al, ). In the following section, the relevance of ISP as a model of MI has been detailed.…”

Section: Introductionmentioning

confidence: 99%

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Allawadhi

Khurana

Sayed

et al. 2018

Phytotherapy Research

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Heart is the most active and incumbent organ of the body, which maintains blood flow, but due to various pathological reasons, several acute and chronic cardiac complications arise out of which myocardial infarction is one of the teething problems. Isoproterenol (ISP)-induced myocardial ischemia is a classical model to screen the cardioprotective effects of various pharmacological interventions. Phytochemicals present a novel option for treating various human maladies including those of the heart. A large number of plant products and their active ingredients have been screened for efficacy in ameliorating ISP-induced myocardial ischemia including coriander, curcumin, Momordica, quercetin, and Withania somnifera. These phytochemicals constituents may play key role in preventing disease and help in cardiac remodeling. Reactive oxygen species scavenging, antiinflammatory, and modulation of various molecular pathways such as Nrf2, NFкB, p-21 activated kinase 1 (PAK1), and p-smad2/3 signaling modulation have been implicated behind the claimed protection. In this review, we have provided a focused overview on the utility of ISP-induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis for preclinical research. In addition, we have also surveyed molecular mechanism of various plant-based interventions screened for cardioprotective effect in ISP-induced cardiotoxicity, and their probable mechanistic profile is summarized.

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Transgenic overexpression of transient receptor potential vanilloid subtype 1 attenuates isoproterenol-induced myocardial fibrosis in mice

Cited by 17 publications

References 42 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

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

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