IL-6 inhibitors effectively reverse post-infarction cardiac injury and ischemic myocardial remodeling via the TGF-[beta]1/Smad3 signaling pathway

• Published in: Experimental and therapeutic medicine Vol. 24; no. 3
• Main Authors: Wang, Jiahong, Wang, Minghong, Lu, Xiancheng, Zhang, Yi, Zeng, Siliang, Pan, Xin, Zhou, Yimeng, Wang, Hui, Chen, Nannan, Cai, Fengfeng, Biskup, Ewelina
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.09.2022
• Subjects: Cardiomyopathy; Complications and side effects; Development and progression; Drug therapy; Health aspects; Heart attack; Heart diseases; Interleukin-6; Physiological aspects; Risk factors; Smad proteins; Transforming growth factors; China
• ISSN: 1792-0981
• DOI: 10.3892/etm.2022.11513

Approximately one in four myocardial infarctions occur in older patients. The majority of therapeutic advances are either not appropriate or not tested in elderly patients. The main reasons for deviating from the guidelines are justified concerns regarding the effectiveness of the recommended forms of therapy, fear of adverse drug reactions and ethical concerns. Targeting interleukin 6 (IL-6) for ventricular remodeling after cardiovascular damage is a feasible alternative to standard polypharmaceutics, but the underlying molecular mechanisms are not well understood. Continuous activation of the IL-6-associated cytokine receptor gp130 leads to cardiomyopathic hypertrophy. TGF[beta]1 is involved in forming fibrosis in various organs, and its overexpression can cause myocardial hypertrophy and fibrosis. Il-6 has been hypothesized to be indirectly involved in cardiac remodeling via the TGF[beta]1/Smad signaling transduction pathway. In the present study, a rat model of acute myocardial ischemia, IL-6 and IL-6 receptor blockers were injected directly into the necrotic myocardium. Changes in cardiac function, myocardial infarction area, myocardial collagen, necrotic myocardial fibrosis and levels of TGF[beta]1, IL-6 and MMP2/9 were quantified in myocardial tissue fibrosis by ELISA. The present study demonstrated that IL-6 stimulated myocardial fibrosis through the TGF[beta]1-Smad-MM2/9 signaling transduction pathway. Overall, this provided a solid foundation for understanding the relationship between IL-6 and ventricular remodeling. Key words: interleukin 6, interleukin 6 inhibitor, myocardial infarction, rejuvenation, TGF[beta]1/Smad3, ventricular remodeling