Protective effects of rolipram on endotoxic cardiac dysfunction via inhibition of the inflammatory response in cardiac fibroblasts

Ji, Jingjing; Liu, Zhifeng; Hong, Xinxin; Liu, Zheying; Gao, Jinghua; Liu, Jinghua

doi:10.1186/s12872-020-01529-7

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…AngII-induced cardiac remodeling is characterized by a pathophysiological response to chronic inflammation with progressive fibrosis (Zhao et al, 2019;Lin et al, 2021). In this process, an inflammatory milieu can promote the phenotypic transformation of cardiac fibroblasts (Ji et al, 2020). AngII is known to have a strong proinflammatory and reported profibrotic effects on facilitating the synthesis of ECM and further contributing to myocardial fibrosis with increased expression of cytokines such as IL-1β, IL-6, and TNF-α (She et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway

Zhao

Zhang

et al. 2021

J. Zhejiang Univ. Sci. B

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Objective: Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms. Methods: We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods. Results: Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent. Conclusions: These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway

Zhao

Zhang

et al. 2021

J. Zhejiang Univ. Sci. B

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“…They promote a response to insult in association with the immune system. Bacteria can trigger fibroblasts to produce inflammatory mediators (cytokines, chemokines, and growth factors) that recruit inflammatory cells from the circulation, amplifying the inflammatory process and inducing heart dysfunction through atherogenesis [ 36 , 37 , 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial Peptides Active in In Vitro Models of Endodontic Bacterial Infections Modulate Inflammation in Human Cardiac Fibroblasts

et al. 2022

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Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial resistances are a major threat, the use of standard antibiotics is not recommended when the infection is only local. Antimicrobial peptides were recently demonstrated to be valid alternatives for dental treatments. The antimicrobial peptide M33D is a tetrabranched peptide active against Gram-negative and Gram-positive bacteria. It has a long life, unusual for peptides, because its branched form provides resistance to proteases. Here the efficacy of M33D and of its analog M33i/l as antibiotics for local use in dentistry was evaluated. M33D and M33i/l were active against reference strains and multidrug-resistant clinical isolates of Gram-negative and Gram-positive species. Their minimum inhibitory concentration against different strains of dental interest was between 0.4 and 6.0 μM. Both peptides acted rapidly on bacteria, impairing membrane function. They also disrupted biofilm effectively. Disinfection of the root canal is crucial for endodontic treatments. M33D and M33i/l reduced E. faecalis colonies to one-twentieth in a dentin slices model reproducing root canal irrigation. They both captured and neutralized lipopolysaccharide (LPS), a bacterial toxin responsible for inflammation. The release of IL-1β and TNFα by LPS-stimulated murine macrophages was reduced by both peptides. Human cardiac fibroblasts respond to different insults with the release of proinflammatory cytokines, and consequently, they are considered directly involved in atherogenic cardiovascular processes, including those triggered by infections. The presence of M33D and M33i/l at MIC concentration reduced IL6 release from LPS- stimulated human cardiac fibroblasts, hence proving to be promising in preventing bacteria-induced atherogenesis. The two peptides showed low toxicity to mammalian cells, with an EC50 one order of magnitude higher than the average MIC and low hemolytic activity. The development of antimicrobial peptides for dental irrigations and medication is a very promising new field of research that will provide tools to fight dental infections and their severe consequences, while at the same time protecting standard antibiotics from new outbreaks of antimicrobial resistance.

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“…1 An increasing number of studies have shown that CFs secrete both proinflammatory and antiinflammatory cytokines involved in cardiac inflammation. 2 The proinflammatory cytokines, IL-1b, IL-6, and TNF-a, can regulate the differentiation of CFs into myofibroblasts 3,4 and the secretion of various MMPs and TIMP-1, as well as promote extracellular matrix deposition. 5 However, IL-10 can reduce fibrosis by inhibiting the proliferation of rat CFs.…”

Section: Introductionmentioning

confidence: 99%

Serelaxin Inhibits Lipopolysaccharide-induced Inflammatory Response in Cardiac Fibroblasts by Activating Peroxisome Proliferator-activated Receptor-γ and Suppressing the Nuclear Factor-Kappa B Signaling Pathway

Wu¹,

Lv²,

Li³

et al. 2023

Journal of Cardiovascular Pharmacology

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Serelaxin has an inhibitory effect on fibrosis. However, whether the anti-fibrotic effects of serelaxin are achieved by inhibiting the inflammatory response has not been clarified. This study aimed to investigate the role of serelaxin in lipopolysaccharide (LPS)-induced inflammation in cardiac fibroblasts (CFs) and elucidate the underlying mechanisms.CFs were isolated from adult rat hearts. The effect of serelaxin on the inhibition of the inﬂammatory response after LPS induction was examined. Cell viability was measured by MMT assay. Cell proliferation was determined using the cell-counting kit-8. The levels of inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-10 were measured using an enzyme-linked immunosorbent assay (ELISA). The mRNA levels of α-SMA, collagen I/III, MMP-2, MMP-9, IL-1β, IL-6,TNF-α, IL-10, IκBα, p-IκBα, p65 subunit of nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed by real-time quantitative PCR (RT-qPCR). The protein levels of α-SMA, collagen I/III, MMP-2, MMP-9, IκBα, p-IκBα, p65, p-p65 and PPAR-γ were examined by western blotting.Serelaxin inhibited LPS-induced IL-1β, IL-6, TNF-α, α-SMA, and collagen I/III, and elevated the expression of IL-10, MMP-2 and MMP-9. Moreover, LPS-induced activation of NF-κB pathway was suppressed by serelaxin treatment. Further studies showed that serelaxin did not significantly increase the expression of PPAR-γ mRNA and protein, but activated PPAR-γ activity, and the PPAR-γ inhibitor GW9662 reversed the inhibitory effect of serelaxin on IL-1β, IL-6, and TNF-α production. These results suggest that serelaxin alleviates cardiac fibrosis by stimulating PPAR-γ via a ligand-independent mechanism which subsequently abolish the expression of NF-κB signalling pathway.

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Protective effects of rolipram on endotoxic cardiac dysfunction via inhibition of the inflammatory response in cardiac fibroblasts

Cited by 6 publications

References 47 publications

Low-intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway

Low-intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway

Antimicrobial Peptides Active in In Vitro Models of Endodontic Bacterial Infections Modulate Inflammation in Human Cardiac Fibroblasts

Serelaxin Inhibits Lipopolysaccharide-induced Inflammatory Response in Cardiac Fibroblasts by Activating Peroxisome Proliferator-activated Receptor-γ and Suppressing the Nuclear Factor-Kappa B Signaling Pathway

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