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Cardiotrophin-1 Deficiency Abrogates Atherosclerosis Progression
Kapka Miteva1, Daniela Baptista1, Fabrizio Montecucco2,3
1Division of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211, Geneva 4, Switzerland.
Scientific Reports
|April 3, 2020
Summary
Cardiotrophin-1 (CT-1) deficiency reduces atherosclerosis in mice by lowering cholesterol and improving plaque stability. This involves promoting anti-inflammatory immune cells and regulating key signaling factors, ultimately halting disease progression.
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- Cardiotrophin-1 (CT-1) is implicated in cardiovascular diseases.
- Atherosclerosis is a chronic inflammatory disease of the arteries.
Purpose of the Study:
- To investigate the role of CT-1 deficiency in atherosclerosis development and progression.
- To analyze the impact of CT-1 deficiency on lipid profiles, plaque characteristics, immune cell responses, and paracrine factors in a mouse model.
Main Methods:
- Utilized double knockout Apoe-/-ct-1-/- mice and control Apoe-/- mice fed normal or high-cholesterol diets.
- Quantified serum lipids, intraplaque content, and immune cell populations via flow cytometry.
- Analyzed systemic paracrine factors and aortic sections for atherosclerotic burden.
Main Results:
- Apoe-/-ct-1-/- mice showed reduced total cholesterol, LDL-C, and atherosclerotic plaque size.
- CT-1 deficiency improved plaque stability and promoted atheroprotective immune responses, including increased regulatory T cells, regulatory B cells, and B1a cells.
- CT-1 deficiency modulated specific paracrine factors (IL-3, IL-6, IL-9, IL-15, IL-27, CXCL5, MCP-3, MIP-1α, MIP-1β) associated with anti-inflammatory effects.
Conclusions:
- CT-1 deficiency confers significant anti-atherosclerotic effects in a mouse model.
- Targeting CT-1 may represent a novel therapeutic strategy for managing atherosclerosis and cardiovascular diseases.
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