Related Experiment Video
Updated: Dec 15, 2025
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Cardiac apoptosis caused by elevated cholesterol level in experimental autoimmune myocarditis
He Chang1, Yue Wang2, Yang Wu2
1School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Geriatrics, Xiang'an Hospital of Xiamen University, Xiamen, 361100, China.
Insights
Cholesterol reduction in heart tissue ameliorates experimental autoimmune myocarditis (EAM) by reducing cardiac apoptosis. This study shows cholesterol-lowering agents may treat myocarditis by targeting cardiac cholesterol, not just plasma levels.
Area of Science:
- Cardiology
- Molecular Biology
- Pathology
Background:
- Cholesterol-lowering agents may treat myocarditis, but their benefit is debated as plasma cholesterol levels often remain unchanged.
- Experimental autoimmune myocarditis (EAM) is an inflammatory heart condition where cardiac cholesterol dynamics are poorly understood.
Purpose of the Study:
- To investigate the role of cardiac cholesterol metabolism in EAM.
- To evaluate the therapeutic potential of cholesterol depletion in EAM.
Main Methods:
- Utilized experimental autoimmune myocarditis (EAM) in rats.
- Administered methyl-β-cyclodextrin (MβCD), a cholesterol-depleting agent.
- Assessed cardiac function, inflammation, collagen deposition, and apoptosis markers.
Main Results:
- EAM induced elevated cardiac cholesterol and impaired cholesterol efflux, with reduced serum high-density lipoprotein (HDL) and Paraoxonase 1 (PON1) activity.
- MβCD treatment alleviated EAM severity, indicated by improved heart weight-to-body weight ratio, reduced inflammation and fibrosis, and enhanced cardiac function.
- MβCD treatment reduced pro-apoptotic proteins (Bax, Fas, FasL, caspase-3) and increased anti-apoptotic protein (Bcl-2) in cardiac tissue.
Conclusions:
- Cardiac cholesterol accumulation and impaired efflux are key features of EAM.
- Cholesterol depletion in cardiac tissue effectively suppresses EAM progression and cardiac apoptosis.
- Targeting cardiac cholesterol may be a novel therapeutic strategy for myocarditis.
Abstract:
It has been reported that cholesterol-lowing agents can ameliorate severity of myocarditis. However, the beneficial effect of the agents has been claimed to be independent of cholesterol reduction as there is no significant change in the plasma cholesterol level in myocarditis. In the present study, using experimental autoimmune myocarditis (EAM) rats as an animal model, we demonstrated that EAM induced elevation of cholesterol level and impaired cholesterol efflux capacity in the cardiac tissue. Moreover, serum high-density lipoprotein (HDL) content was reduced and HDL function associated protein Paraoxonase 1 (PON1) activity was decreased. Besides, the major structural protein within HDL, Apolipoprotein A1 (ApoA1) expression in the cardiac tissues was significantly reduced while the level of serum ApoA1 was not significantly altered. Importantly, cholesterol depleting agent methyl-β-cyclodextrin (MβCD) alleviated the development of EAM, as monitored by decreased ratio of heart weight to body weight (HW/BW), decreased infiltration of inflammatory cells and collagen deposition, improved cardiac function, reduced expression of apoptosis-related protein Bax, Fas, FasL and caspase-3 and increased level of anti-apoptotic protein Bcl-2. These results suggest that reduction of cholesterol level in cardiac tissue could suppress EAM-induced cardiac apoptosis through both intrinsic and extrinsic apoptotic pathways.
Related Concept Videos
01:21Myocarditis I: Introduction
01:27Myocarditis II: Clinical Features and Diagnostic Tests