Abstract
Myocardial hypertrophy plays an essential role in the structural remodeling of the heart and the progression to heart failure (HF). There is an urgent need to understand the mechanisms underlying cardiac hypertrophy and to develop treatments for early intervention. Dangshen Erling decoction (DSELD) is a clinically used formula in Chinese medicine for treating coronary heart disease in patients with HF. However, the mechanism by which DSELD produces its cardioprotective effects remains largely unknown. This study explored the effects of DSELD on myocardial hypotrophy both in vitro and in vivo. In vitro studies indicated that DSELD significantly (p < 0.05) reduced the cross-sectional area of the myocardium and reduced elevated lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels in the induced H9C2 cell model to study inflammation. In vivo experiments revealed that DSELD restores cardiac function and significantly reduces myocardial fibrosis in isoproterenol (ISO)-induced HF mouse model (p < 0.05). In addition, DSELD downregulated the expression of several inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), IL-1α, IL-1β, IL-3, IL-5, IL-7, IL-12, IL-13, and TNF-α in HF (p < 0.05). Further analysis of the cardiac tissue demonstrated that DSELD produces its anti-inflammatory effects via the Toll-like receptor (TLR)4 signaling pathway. The expression of TLR4 downstream proteins such as matrix metalloproteinase-9 (MMP9) and myeloid differentiation factor-88 (MyD88) was among the regulated targets. In conclusion, these observations suggest that DSELD exerts antihypertrophic effects by alleviating the inflammatory injury via the TLR4 signaling pathway in HF and thus holds promising therapeutic potentials.
Highlights
Heart failure (HF) is one of the most common forms of cardiac dysfunction caused by various cardiac diseases such as coronary heart disease, hypertension, arrhythmia, and viral myocarditis
The results demonstrate that Dangshen Erling decoction (DSELD) ameliorates myocardial hypertrophy via inhibiting the TLR4-mediated myocardial inflammation
To evaluate the effects of DSELD on cardiac hypertrophy, DSELD was intragastrically administered at a dose of 1.28 g/kg in the ISOinduced mouse model for 4 weeks (Figure 1A)
Summary
Heart failure (HF) is one of the most common forms of cardiac dysfunction caused by various cardiac diseases such as coronary heart disease, hypertension, arrhythmia, and viral myocarditis. HF is characterized by consistent pathological myocardial hypertrophy leading to increasing mortality and morbidity worldwide (Adamo et al, 2020). Pathological myocardial hypertrophy is characterized by enlarged cardiomyocytes and thickened ventricular walls that are the typical features of cardiac. Dangshen Erling Decoction and Myocardial Hypertrophy remodeling in HF (Tham et al, 2015). This adaptive change is to maintain the normal ejection fraction of the heart under increased pressure load; sustained pathological overload induces these changes to progress gradually into irreversible damage to the cardiac structure and function (Oka et al, 2014). Sustained myocardial hypertrophy is the key to HF. Several studies suggest that persistent myocardial inflammation is the hallmark of myocardial hypertrophy (Geng et al, 2019; Zhang et al, 2020b; Zhu et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
