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Exogenous IL-19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction.

ABSTRACT: BACKGROUND AND PURPOSE:Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin-19 (IL-19) in mice with MI and investigated the underlying molecular mechanism. EXPERIMENTAL APPROACH:Mice were subjected to MI by ligation of left anterior descending coronary artery (LAD) and treated with IL-19 (10ng g-1 ; i.p.). KEY RESULTS:Protein expression of IL-19 and its receptor in myocardium were upregulated 24 hrs post-MI in male mice. IL-19 treatment decreased infarct and apoptosis in myocardium, accompanied by enhanced haem oxygenase-1 (HO-1) activities and reduced malondialdehyde (MDA) formation. Pretreatment with IL-19 upregulated HO-1 expression in cultured neonatal mouse ventricular myocytes and attenuated oxygen-glucose deprivation (OGD)-induced injuries in vitro. Furthermore, IL-19 preserved cardiac function and improved survival of mice with MI. IL-19 reduced inflammatory infiltrates and suppressed formation of TNF-?, IL-1?, and IL-6. More importantly, IL-19 inhibited polarization toward proinflammatory M1 macrophages and stimulated M2 macrophage polarization in myocardium of mice with MI. IL-19 enhanced protein levels of vascular endothelial growth factor (VEGF) and promoted angiogenesis in myocardium of mice with MI. In addition, IL-19 treatment increased DNA-binding of the transcription factor STAT3 in myocardium of mice with MI. CONCLUSIONS AND IMPLICATIONS:Treatment with exogenous IL-19 attenuated acute ischemic injury and improved survival of mice with MI. The mechanisms underlying these effects involved induction of HO-1, M2 macrophage polarization, angiogenesis, and STAT3 activation.

SUBMITTER: An W

PROVIDER: S-EPMC6365357 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Exogenous IL-19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction.

An Weishuai W Yu Yongsheng Y Zhang Yuefan Y Zhang Zhigang Z Yu Yunhua Y Zhao Xianxian X

British journal of pharmacology 20190108 5

<h4>Background and purpose</h4>Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin-19 (IL-19) in mice with MI and investigated the underlying molecular mechanism.<h4>Experimental approach</h4>Mice were subjected to MI by ligation of left anterior descending coronary artery (LAD) and treated with IL-19 (10ng g<sup>-1</sup> ; i.p.).<h4>Key results</h4>Protein exp ...[more]

PMID: 30460984

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Project description:AimTo examine the contribution of treatment resistant depression (TRD) to mortality in depressed post-myocardial infarction (MI) patients independent of biological and social predictors.MethodsThis secondary analysis study utilizes the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial data. From 1834 depressed patients in the ENRICHD study, there were 770 depressed post-MI patients who were treated for depression. In this study, TRD is defined as having a less than 50% reduction in Hamilton Depression (HAM-D) score from baseline and a HAM-D score of greater than 10 in 6 mo after depression treatment began. Cox regression analysis was used to examine the independent contributions of TRD to mortality after controlling for the biological and social predictors.ResultsTRD occurred in 13.4% (n = 103) of the 770 patients treated for depression. Patients with TRD were significantly younger in age (P = 0.04) (mean = 57.0 years, SD = 11.7) than those without TRD (mean = 59.2 years, SD = 12.0). There was a significantly higher percentage of females with TRD (57.3%) compared to females without TRD (47.4%) [χ(2) (1) = 4.65, P = 0.031]. There were significantly more current smokers with TRD (44.7%) than without TRD (33.0%) [χ(2) (1) = 7.34, P = 0.007]. There were no significant differences in diabetes (P = 0.120), history of heart failure (P = 0.258), prior MI (P = 0.524), and prior stroke (P = 0.180) between patients with TRD and those without TRD. Mortality was 13% (n = 13) in patients with TRD and 7% (n = 49) in patients without TRD, with a mean follow-up of 29 mo (18 mo minimum and maximum of 4.5 years). TRD was a significant independent predictor of mortality (HR = 1.995; 95%CI: 1.011-3.938, P = 0.046) after controlling for age (HR = 1.036; 95%CI: 1.011-1.061, P = 0.004), diabetes (HR = 2.912; 95%CI: 1.638-5.180, P < 0.001), heart failure (HR = 2.736; 95%CI: 1.551-4.827, P = 0.001), and smoking (HR = 0.502; 95%CI: 0.228-1.105, P = 0.087).ConclusionThe analysis of TRD in the ENRICHD study shows that the effective treatment of depression reduced mortality in depressed post-MI patients. It is important to monitor the effectiveness of depression treatment and change treatments if necessary to reduce depression and improve cardiac outcomes in depressed post-MI patients.

Project description:Myocardial fibrosis is a major determinant of clinical outcomes in heart failure (HF) patients. It is characterized by the emergence of myofibroblasts and early activation of pro-fibrotic signaling pathways before adverse ventricular remodeling and progression of HF. Boron has been reported in recent years to augment the innate immune system and cell proliferation, which play an important role in the repair and regeneration of the injured tissue. Currently, the effect of boron on cardiac contractility and remodeling is unknown. In this study, we investigated, for the first time, the effect of boron supplementation on cardiac function, myocardial fibrosis, apoptosis and regeneration in a rat model myocardial infarction (MI)-induced HF. MI was induced in animals and borax, a sodium salt of boron, was administered for 7 days, p.o., 21 days post-injury at a dose level of 4 mg/kg body weight. Transthoracic echocardiographic analysis showed a significant improvement in systolic and diastolic functions with boron treatment compared to saline control. In addition, boron administration showed a marked reduction in myocardial fibrosis and apoptosis in the injured hearts, highlighting a protective effect of boron in the ischemic heart. Interestingly, we observed a tenfold increase of nuclei in thin myocardial sections stained positive for the cell cycle marker Ki67 in the MI boron-treated rats compared to saline, indicative of increased cardiomyocyte cell cycle activity in MI hearts, highlighting its potential role in regeneration post-injury. We similarly observed increased Ki67 and BrdU staining in cultured fresh neonatal rat ventricular cardiomyocytes. Collectively, the results show that boron positively impacted MI-induced HF and attenuated cardiac fibrosis and apoptosis, two prominent features of HF. Importantly, boron has the potential to induce cardiomyocyte cell cycle entry and potentially cardiac tissue regeneration after injury. Boron might be beneficial as a supplement in MI and may be a good candidate substance for anti-fibrosis approach.

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Exogenous IL-19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction.

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Exogenous IL-19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction.

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