Angiotensin II-induced mitochondrial reactive oxygen species and peroxiredoxin-3 expression in cardiac fibroblasts

Lijnen, Paul; Piccart, Yvette; Coenen, Tamara; Prihadi, John S.

doi:10.1097/hjh.0b013e32835726c1

Cited by 14 publications

(5 citation statements)

References 43 publications

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“…In the present study, TRPM7 expression was increased in SAN tissues in SSS rats together with a significant increase in Smad2 phosphorylation level, suggesting the involvement of TRPM7/Smad2 in Ang II-mediated myocardial fibrosis. Many clinical studies have demonstrated that Ang II contributes to the cardiac remodeling that occurs in hypertensive heart disease, heart failure, myocardial infarction, cardiomyopathy, and paroxysmal atrial fibrillation with sick sinus syndrome [ 35 – 38 ]. In addition, Ang II expression is more pronounced in myocardial tissue with elevated cardiac load due to fibrosis than in normal myocardial tissues and is closely related to interstitial fibrosis in myocardium [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling

et al. 2018

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Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown. The aim of this study was to investigate the role of angiotensin II (Ang II)/TRPM7/Smad pathway in the SAN fibrosis in rats with SSS. The rat SSS model was established with sodium hydroxide pinpoint pressing permeation. Forty-eight rats were randomly divided into six groups: normal control (ctrl), sham operation (sham), postoperative 1-, 2-, 3-, and 4-week SSS, respectively. The tissue explant culture method was used to culture cardiac fibroblasts (CFs) from rat SAN tissues. TRPM7 siRNA or encoding plasmids were used to knock down or overexpress TRPM7. Collagen (Col) distribution in SAN and atria was assessed using PASM–Masson staining. Ang II, Col I, and Col III levels in serum and tissues or in CFs were determined by ELISA. TRPM7, smad2 and p-smad2 levels were evaluated by real-time PCR, and/or western blot and immunohistochemistry. SAN and atria in rats of the SSS groups had more fibers and higher levels of Ang II, Col I and III than the sham rats. Similar findings were obtained for TRPM7 and pSmad2 expression. In vitro, Ang II promoted CFs collagen synthesis in a dose-dependent manner, and potentiated TRPM7 and p-Smad2 expression. TRPM7 depletion inhibited Ang II-induced p-Smad2 expression and collagen synthesis in CFs, whereas increased TRPM7 expression did the opposite. SAN fibrosis is regulated by the Ang II/TRPM7/Smad pathway in SSS, indicating that TRPM7 is a potential target for SAN fibrosis therapy in SSS.

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Section: Discussionmentioning

confidence: 99%

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling

et al. 2018

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“…At the subcellular level, Prdx1 and Prdx2 were found throughout the cell, while Prdx3 and Prdx5 were primarily mitochondrial, some nuclear labeling was observed. Recent studies point to the importance of Prdxs to exert protective antioxidant effects in various cells [ 28 , 29 ]. However, the physiological effects and the underlying mechanisms of Prdxs in renal fibrosis have not been fully characterized.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 5 Protects TGF-β Induced Fibrosis by Inhibiting Stat3 Activation in Rat Kidney Interstitial Fibroblast Cells

et al. 2016

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Renal fibrosis is a common final pathway of end-stage kidney disease which is induced by aberrant accumulation of myofibroblasts. This process is triggered by reactive oxygen species (ROS) and proinflammatory cytokines generated by various source of injured kidney cells. Peroxiredoxin 5 (Prdx5) is a thiol-dependent peroxidase that reduces oxidative stress by catalyzing intramolecular disulfide bonds. Along with its antioxidant effects, expression level of Prdx5 also was involved in inflammatory regulation by immune stimuli. However, the physiological effects and the underlying mechanisms of Prdx5 in renal fibrosis have not been fully characterized. Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO) for 1 or 7 days. For the in vitro model, NRK49F cells, a rat kidney interstitial fibroblast cell lines, were treated with transforming growth factor β (TGF-β) for 0, 1, 3, or 5 days. To access the involvement of its peroxidase activity in TGF-β induced renal fibrosis, wild type Prdx5 (WT) and double mutant Prdx5 (DM), converted two active site cysteines at Cys 48 and Cys 152 residue to serine, were transiently expressed in NRK49F cells. The protein expression of Prdx5 was reduced in UUO kidneys. Upregulation of fibrotic markers, such as fibronectin and alpha-smooth muscle actin (α-SMA), declined at 5 days in time point of higher Prdx5 expression in TGF-β treated NRK49F cells. The overexpression of wild type Prdx5 by transient transfection in NRK49F cells attenuated the TGF-β induced upregulation of fibronectin and α-SMA. On the other hand, the transient transfection of double mutant Prdx5 did not prevent the activation of fibrotic markers. Overexpression of Prdx5 also suppressed the TGF-β induced upregulation of Stat3 phosphorylation, while phosphorylation of Smad 2/3 was unchanged. In conclusion, Prdx5 protects TGF-β induced fibrosis in NRK49F cells by modulating Stat3 activation in a peroxidase activity dependent manner.

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“…The rennin-angiotensin system plays a central role in cardiac structural remodeling and in the development of myocardial fibrosis in several disease states including CHF [47], myocardial infarction [48], and cardiomyopathy [49]. ROS production is elevated by AngII and hypertension [50, 51]. In response to hypoxia, fibroblasts differentiate to myofibroblasts [52], thereby initiating the fibrotic process.…”

Section: Signaling Pathways Involved In Cardiac Fibrosismentioning

confidence: 99%

Transient Receptor Potential (TRP) Channels and Cardiac Fibrosis

Yue¹,

Zhang²,

Xie³

et al. 2013

CTMC

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Cardiac fibrosis is associated with most cardiac diseases. Fibrosis is an accumulation of excessive extracellular matrix proteins (ECM) synthesized by cardiac fibroblasts and myofibroblasts. Fibroblasts are the most prevalent cell type in the heart, comprising 75% of cardiac cells. Myofibroblasts are hardly present in healthy normal heart tissue, but appear abundantly in diseased hearts. Cardiac fibroblasts are activated by a variety of pathological stimuli, such as myocardial injury, oxidative stress, mechanical stretch, and elevated autocrine-paracrine mediators, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. A number of signaling pathways and bioactive molecules are involved and work in concert to activate fibroblasts and myofibroblasts in the fibrogenesis cascade. Fibroblasts and myofibroblasts are not only principal ECM producers, but also play a central role in fibrogenesis and myocardial remodeling in fibrotic heart disease. Thus, understanding the biological processes of cardiac fibroblasts will provide novel insights into the underlying mechanisms of fibrosis and provide potential targets for developing anti-fibrotic drugs. Recent studies demonstrate that Ca2+ signal is essential for fibroblast proliferation, differentiation, and ECM-protein production. This review focuses on the recent advances in understanding molecular mechanisms of Ca2+ signaling in cardiac fibrogenesis, and potential role of Ca2+-permeable channels, in particular, the transient potential (TRP) channels in fibrotic heart disease. TRP channels are highly expressed in cardiac fibroblasts. TRPM7 has been shown to be essential in TGFβ1 mediated fibrogenesis, and TRPC3 has been demonstrated to play an essential role in regulating fibroblast function. Thus, the Ca2+-permeable TRP channels may serve as potential novel targets for developing anti-fibrotic drugs.

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Angiotensin II-induced mitochondrial reactive oxygen species and peroxiredoxin-3 expression in cardiac fibroblasts

Abstract: Our data indicate that ANG II-stimulated mitochondrial reactive oxygen species production in rat cardiac fibroblasts is accompanied by a reduction in the expression of the mitochondrial antioxidant Prx-3, and thereby potentially contributing to oxidative stress in the myocard.

Cited by 14 publications

References 43 publications

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling

Peroxiredoxin 5 Protects TGF-β Induced Fibrosis by Inhibiting Stat3 Activation in Rat Kidney Interstitial Fibroblast Cells

Transient Receptor Potential (TRP) Channels and Cardiac Fibrosis

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