Synthetic CpG oligonucleotides induce a genetic profile ameliorating murine myocardial I/R injury

Hilbert, Tobias; Markowski, Paul; Frede, Stilla; Boehm, Olaf; Knuefermann, Pascal; Baumgarten, Georg; Hoeft, Andreas; Klaschik, Sven

doi:10.1111/jcmm.13616

Cited by 8 publications

(7 citation statements)

References 66 publications

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“…The observed LV dysfunction in CD mice after reperfused MI is in accordance with previous studies from our groups and others [44][45][46][47][48]. However, in the present study, DHA supplementation beginning 7 days prior to MI resulted in sustained systolic and diastolic LV function that was characterized by lower end-diastolic pressure (EDP), greater ejection fraction (EF), and reduced isovolumetric relaxation (Tau) 14 d after 60 min LAD occlusion compared to CD-fed mice, with no difference in end-systolic blood pressures.…”

Section: Discussionsupporting

confidence: 92%

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

Habicht

Mohsen

Eichhorn

et al. 2020

Oxidative Medicine and Cellular Longevity

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Objective. Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. Methods. C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. Results. DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3±0.4 CD vs. 1.4±0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0±0.6 CD vs. 1.5±0.2 DHA), IL-1β (60.7±7.0 CD vs. 11.6±1.9 DHA), and IL-10 (223.8±62.1 CD vs. 135.5±38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/β myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8±11.5 CD vs. 78.8±13.6 DHA) but terminated earlier (CCL2 72 h: 39.5±7.8 CD vs. 8.2±1.9 DHA; CCL3 72 h: 794.3±270.9 CD vs. 258.2±57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6±2.6 CD vs. 31.4±1.5 DHA). Conclusion. Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to β-MHC isoform switch.

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Section: Discussionsupporting

confidence: 92%

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

Habicht

Mohsen

Eichhorn

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In particular, JAK1 and JAK2 were activated by MI/RI, which in turn activates STAT1 and STAT3, STAT1 promotes apoptosis, whilst STAT3 protects cardiomyocyte (Stephanou 2004). Apoptosis is a crucial pathophysiological feature in the early I/R that triggers more severe heart failure (Hilbert et al 2018). Hattori et al (2001) found that activated JAK/STAT up-regulated Bcl-2 and down-regulated Bax, enhancing myocardial pro-survival pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis is a crucial pathophysiological feature in the early I/R that triggers more severe heart failure (Hilbert et al. 2018 ). Hattori et al.…”

Section: Discussionmentioning

confidence: 99%

Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

Song

2020

Pharmaceutical Biology

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Context: Baicalin is an active compound which demonstrates cardioprotection effects against myocardial ischaemia/reperfusion injury (MI/RI). Objective: To investigate how baicalin protects against myocardial injury and to explore its potential mechanism. We hypothesized that baicalin-modulated macrophages change from M1 (pro-inflammatory subset) to M2 (anti-inflammatory subset) under I/R stress. Materials and methods: We established an ischaemia/reperfusion (I/R) model using Sprague Dawley (SD) rat, then baicalin was intragastric administration (20, 60 or 120 mg/kg) for 24 h. The rats were randomly divided into five groups (n ¼ 10): control, I/R, I/R þ baicalin (20 mg/kg), I/R þ baicalin (60 mg/kg) and I/R þ baicalin (120 mg/kg). Cardiac function was detected by echocardiography, HE staining and ELISA, respectively. Macrophage phenotype was examined by flow cytometry. Furthermore, IHC, qRT-PCR and WB were employed to analyse the related mechanisms. Results: The study showed that baicalin (20, 60 or 120 mg/kg) significantly improved cardiac function and impeded cardiac apoptosis in rats. In addition, the repair of myocardial morphology (reduced neutrophil infiltration) further confirmed its cardiacprotective effect. Moreover, baicalin effectively decreased iNOS, IL-1b and IL-6, and up-regulated Arg-1, IL-10 and TGF-b via changing the macrophage phenotype (from M1 towards M2). Notably, treatment with baicalin also inhibited the phosphorylation levels of JAK2 and STAT3. Discussion and conclusions: It was confirmed that baicalin alleviated post-I/R myocardial injury and reduced inflammation via JAK/STAT pathway, and baicalin treatment might be recommended as a new approach for myocardial ischaemic complications.

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“…The mouse heart was exposed by a left‐sided thoracotomy. The left anterior descending coronary artery (LAD) was ligated for 45 minutes with a 7/0 silk thread followed by reopening of the artery for 24 hours . The mice in sham group underwent a same procedure, but with no LAD ligation.…”

Section: Methodsmentioning

confidence: 99%

“…The left anterior descending coronary artery (LAD) was ligated for 45 minutes with a 7/0 silk thread followed by reopening of the artery for 24 hours. [16][17][18] The mice in sham group underwent a same procedure, but with no LAD ligation. After I/R procedure, the air was removed from the chest and the surgical wounds were sutured.…”

Section: Mouse Model Of Ischaemia/reperfusionmentioning

confidence: 99%

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

Zhu

Zhuang

et al. 2019

J Cellular Molecular Medi

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Cardiomyocyte apoptosis is an important process occurred during cardiac ischaemia‐reperfusion injury. Long non‐coding RNAs (lncRNA) participate in the regulation of various cardiac diseases including ischaemic reperfusion (I/R) injury. In this study, we explored the potential role of lncRNA ACART (anti‐cardiomyocyte apoptosis‐related transcript) in cardiomyocyte injury and the underlying mechanism for the first time. We found that ACART was significantly down‐regulated in cardiac tissue of mice subjected to I/R injury or cultured cardiomyocytes treated with hydrogen peroxide (H2O2). Knockdown of ACART led to significant cardiomyocyte injury as indicated by reduced cell viability and increased apoptosis. In contrast, overexpression of ACART enhanced cell viability and reduced apoptosis of cardiomyocytes treated with H2O2. Meanwhile, ACART increased the expression of the B cell lymphoma 2 (Bcl‐2) and suppressed the expression of Bcl‐2‐associated X (Bax) and cytochrome‐C (Cyt‐C). In addition, PPAR‐γ was up‐regulated by ACART and inhibition of PPAR‐γ abolished the regulatory effects of ACART on cell apoptosis and the expression of Bcl‐2, Bax and Cyt‐C under H2O2 treatment. However, the activation of PPAR‐γ reversed the effects of ACART inhibition. The results demonstrate that ACART protects cardiomyocyte injury through modulating the expression of Bcl‐2, Bax and Cyt‐C, which is mediated by PPAR‐γ activation. These findings provide a new understanding of the role of lncRNA ACART in regulation of cardiac I/R injury.

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Synthetic CpG oligonucleotides induce a genetic profile ameliorating murine myocardial I/R injury

Cited by 8 publications

References 66 publications

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR‐γ/Bcl‐2 pathway

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