Qiliqiangxin inhibits angiotensin II‐induced transdifferentiation of rat cardiac fibroblasts through suppressing interleukin‐6

Zhou, Jingmin; Jiang, Kun; Ding, Xuefeng; Fu, Mingqiang; Wang, Shijun; Zhu, Liangliang; He, Tao; Wang, Jingfeng; Sun, Aijun; Hu, Kai; Chen, Li; Zou, Yunzeng; Ge, Junbo

doi:10.1111/jcmm.12512

Cited by 21 publications

(18 citation statements)

References 40 publications

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“…Our laboratory and others have reported that QL can attenuate myocardial remodeling and improve cardiac function in rats with experimental myocardial infarction [20-22]. Several studies have mentioned the protective effect of QL on cardiac remodeling, which are associated with inflammation regulation, energy metabolism improvement, and angiogenesis enhancement [23-26], but its mechanism has not been thoroughly elucidated to date. Therefore, using a post-myocardial infarction heart failure model, the present study evaluated the influence of QL on the heart function, cardiac fibrosis, and the expression of TGF-β1, p-Smads, collagen I, TNF-α and IL-6 to further explore whether TGF-β1 and NF-κB pathways are involved in the protective effects of QL during cardiac remodeling.…”

Section: Introductionmentioning

confidence: 99%

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

Han

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

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Section: Introductionmentioning

confidence: 99%

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

Han

Zheng

et al. 2018

Cell Physiol Biochem

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“…Also, it was demonstrated by our group that QL protected against cardiac remodeling after experimental myocardial infarction (MI) or ischemia-reperfusion injury (IRI) via the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) and mTOR, respectively [11,12]. Although a limited number of in vitro studies revealed that QL could enhance the mitochondrial biogenesis in cardiomyocytes, and also inhibit the differentiation of cardiac fibroblasts [13,14], the mechanism underlying the protective effect of QL against cardiac hypertrophy still remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

Zhang¹,

Li²,

Zhou³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.

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“…6 Angiotensin II incubation for 24 hours significantly increased the expression of TGF-b1. 42,43 Thus, we propose that Ang II increases fibrosis by upregulating TGF-b1 and may be mediated with TGF-b/Smad signal pathway. AT1R blockers were shown to suppress TGF-b1 expression in several cell types.…”

Section: Discussionmentioning

confidence: 99%

Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy

Shi

Wang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To examine the effects of losartan on scar formation after trabeculectomy and on fibrotic changes of human Tenon's fibroblasts (HTFs). METHODS.Trabeculectomy was performed on New Zealand rabbits. They were randomized to receive one of the following treatments: 0.9% normal saline, mitomycin-C, or one of the three doses of losartan. Bleb morphology, IOP, and histopathology examination were performed. Primary cultured HTFs were treated with losartan or vehicle, with or without angiotensin II (Ang II). Cell proliferation was assessed by Cell Counting Kit-8 assay, and cell migration was detected by scratch wound and transwell assay. Transdifferentiation was evaluated through the expression of a-smooth muscle actin (a-SMA) by immunofluorescence, real-time PCR, and Western blot. The expression of fibronectin (FN) was evaluated by real-time PCR and Western blot.RESULTS. An amount of 5 mg/mL of losartan subconjunctival injection significantly decreased IOP postoperatively and attenuated wound healing of the filtering bleb in the rabbit model. Immunostaining results showed less myofibroblast and collagen deposition around the bleb area in the losartan-treated eyes. Losartan (10 À5 M) in vitro significantly attenuated Ang II's stimulatory effects on proliferation and migration of HTFs. Expressions of a-SMA and FN in these cells were also decreased by losartan pretreatment.CONCLUSIONS. Losartan attenuates scar formation of filtering bleb after trabeculectomy likely via decreasing proliferation, migration, transdifferentiation, and extracellular matrix deposition of Tenon's fibroblasts. These results indicate that losartan may be an effective therapeutic agent in preventing bleb scar formation and in improving surgical outcome after trabeculectomy.

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Qiliqiangxin inhibits angiotensin II‐induced transdifferentiation of rat cardiac fibroblasts through suppressing interleukin‐6

Cited by 21 publications

References 40 publications

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy

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