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Effect of IL-6-mediated STAT3 signaling pathway on myocardial apoptosis in mice with dilated cardiomyopathy.
Eur Rev Med Pharmacol Sci 2019; 23(7):3042-3050ER

Abstract

OBJECTIVE

To investigate the effect of interleukin-6 (IL-6) gene knockout on apoptosis of myocardial cells in mice with Coxsackievirus B3 (CVB3)-induced dilated cardiomyopathy (DCM) and its potential mechanism, so as to provide certain references for the clinical prevention and treatment of DCM.

MATERIALS AND METHODS

A total of 40 male C57 mice were randomly divided into Sham group (n=20) and DCM group (n=20) using a random number table. Another 20 mice with IL-6 gene knockout were enrolled into DCM+IL-6 KO group (n=20). The DCM model was established via CVB3 repeated incremental infection. After 9 months, the heart weight/body weight (HW/BW) ratio of mice in each group was detected. The ejection fraction [EF (%)] and fraction shortening [FS (%)] of mice in each group were detected via two-dimensional ultrasonography. The cross-sectional area and pathological changes in myocardial cells in the heart in each group were determined using hematoxylin-eosin (HE) staining. The collagen content in myocardial tissues in each group was detected via Masson staining and picrosirius red (PSR) staining, and the expressions of Collagen I and Collagen III in myocardial tissues in each group were detected via immunohistochemistry. In addition, the myocardial apoptosis in myocardial tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and total STAT3 (t-STAT3) were detected via Western blotting.

RESULTS

The expression of IL-6 messenger ribonucleic acids (mRNAs) in myocardial tissues in DCM group was significantly increased compared with that in Sham group (p<0.05). After IL-6 knockout, the HW/BW ratio of DCM mice significantly declined (p<0.05), and the cross-sectional area of myocardial cells was significantly reduced (p<0.05). According to the results of echocardiography, the cardiac function of mice in DCM+IL-6 KO group was significantly superior to that in DCM group, manifested as the significant increase in FS (%) and EF (%) (p<0.05). The results of Masson staining, PSR staining, and immunohistochemical staining showed that IL-6 knockout could reduce the collagen content and Collagen I and Collagen III expressions in myocardial tissues of DCM mice (p<0.05). Furthermore, it was found via TUNEL staining that the number of apoptotic myocardial cells in DCM+IL-6 KO group was markedly smaller than that in DCM group (p<0.05). At the same time, the Bax/Bcl-2 ratio in myocardial tissues in DCM+IL-6 KO group was lower (p<0.05). Finally, the results of Western blotting revealed that DCM+IL-6 KO group had a lower phosphorylation level of STAT3 than DCM group (p<0.05).

CONCLUSIONS

Inhibiting IL-6 gene may improve the DCM-induced myocardial remodeling through reducing myocardial apoptosis.

Authors+Show Affiliations

Department of Geriatrics, Quanzhou First Hospital of Fujian Medical University, Quanzhou, China. drheyafeng@foxmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31002169

Citation

Li, Q, et al. "Effect of IL-6-mediated STAT3 Signaling Pathway On Myocardial Apoptosis in Mice With Dilated Cardiomyopathy." European Review for Medical and Pharmacological Sciences, vol. 23, no. 7, 2019, pp. 3042-3050.
Li Q, Ye WX, Huang ZJ, et al. Effect of IL-6-mediated STAT3 signaling pathway on myocardial apoptosis in mice with dilated cardiomyopathy. Eur Rev Med Pharmacol Sci. 2019;23(7):3042-3050.
Li, Q., Ye, W. X., Huang, Z. J., Zhang, Q., & He, Y. F. (2019). Effect of IL-6-mediated STAT3 signaling pathway on myocardial apoptosis in mice with dilated cardiomyopathy. European Review for Medical and Pharmacological Sciences, 23(7), pp. 3042-3050. doi:10.26355/eurrev_201904_17586.
Li Q, et al. Effect of IL-6-mediated STAT3 Signaling Pathway On Myocardial Apoptosis in Mice With Dilated Cardiomyopathy. Eur Rev Med Pharmacol Sci. 2019;23(7):3042-3050. PubMed PMID: 31002169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of IL-6-mediated STAT3 signaling pathway on myocardial apoptosis in mice with dilated cardiomyopathy. AU - Li,Q, AU - Ye,W-X, AU - Huang,Z-J, AU - Zhang,Q, AU - He,Y-F, PY - 2019/4/20/entrez SP - 3042 EP - 3050 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 23 IS - 7 N2 - OBJECTIVE: To investigate the effect of interleukin-6 (IL-6) gene knockout on apoptosis of myocardial cells in mice with Coxsackievirus B3 (CVB3)-induced dilated cardiomyopathy (DCM) and its potential mechanism, so as to provide certain references for the clinical prevention and treatment of DCM. MATERIALS AND METHODS: A total of 40 male C57 mice were randomly divided into Sham group (n=20) and DCM group (n=20) using a random number table. Another 20 mice with IL-6 gene knockout were enrolled into DCM+IL-6 KO group (n=20). The DCM model was established via CVB3 repeated incremental infection. After 9 months, the heart weight/body weight (HW/BW) ratio of mice in each group was detected. The ejection fraction [EF (%)] and fraction shortening [FS (%)] of mice in each group were detected via two-dimensional ultrasonography. The cross-sectional area and pathological changes in myocardial cells in the heart in each group were determined using hematoxylin-eosin (HE) staining. The collagen content in myocardial tissues in each group was detected via Masson staining and picrosirius red (PSR) staining, and the expressions of Collagen I and Collagen III in myocardial tissues in each group were detected via immunohistochemistry. In addition, the myocardial apoptosis in myocardial tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and total STAT3 (t-STAT3) were detected via Western blotting. RESULTS: The expression of IL-6 messenger ribonucleic acids (mRNAs) in myocardial tissues in DCM group was significantly increased compared with that in Sham group (p<0.05). After IL-6 knockout, the HW/BW ratio of DCM mice significantly declined (p<0.05), and the cross-sectional area of myocardial cells was significantly reduced (p<0.05). According to the results of echocardiography, the cardiac function of mice in DCM+IL-6 KO group was significantly superior to that in DCM group, manifested as the significant increase in FS (%) and EF (%) (p<0.05). The results of Masson staining, PSR staining, and immunohistochemical staining showed that IL-6 knockout could reduce the collagen content and Collagen I and Collagen III expressions in myocardial tissues of DCM mice (p<0.05). Furthermore, it was found via TUNEL staining that the number of apoptotic myocardial cells in DCM+IL-6 KO group was markedly smaller than that in DCM group (p<0.05). At the same time, the Bax/Bcl-2 ratio in myocardial tissues in DCM+IL-6 KO group was lower (p<0.05). Finally, the results of Western blotting revealed that DCM+IL-6 KO group had a lower phosphorylation level of STAT3 than DCM group (p<0.05). CONCLUSIONS: Inhibiting IL-6 gene may improve the DCM-induced myocardial remodeling through reducing myocardial apoptosis. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/31002169/Effect_of_IL-6-mediated_STAT3_signaling_pathway_on_myocardial_apoptosis_in_mice_with_dilated_cardiomyopathy L2 - https://www.europeanreview.org/article/17586 DB - PRIME DP - Unbound Medicine ER -