Related Experiment Video
Updated: May 1, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Targeted mouse complement inhibitor CR2-Crry protects against the development of atherosclerosis in mice
Fengming Liu1, Lin Wu2, Gongxiong Wu3
1Department of Immunology, Shandong University School of Medicine, #44 Wenhua Xi Road, Jinan, Shandong 250012, PR China; Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Objective:
Atherosclerosis is a chronic inflammatory and immune vascular disease, and clinical and experimental evidence has indicated an important role of complement activation products, including the terminal membrane attack complex (MAC), in atherogenesis. Here, we investigated whether complement inhibition represents a potential therapeutic strategy to treat/prevent atherogenesis using CR2-Crry, a recently described complement inhibitor that specifically targets to sites of C3 activation.
Methods And Results:
Previous studies demonstrated that loss of CD59 (a membrane inhibitor of MAC formation) accelerated atherogenesis in Apoe deficient (Apoe(-/-)) mice. Here, both CD59 sufficient and CD59 deficient mice in an Apoe deficient background (namely, mCd59 ab(+/+)/Apoe(-/-) and mCd59 ab(-/-)/Apoe(-/-)) were treated with CR2-Crry for 4 and 2 months respectively, while maintained on a high fat diet. Compared to control treatment, CR2-Crry treatment resulted in significantly fewer atherosclerotic lesions in the aorta and aortic root, and inhibited the accelerated atherogenesis seen in mCd59 ab(+/+)/Apoe(-/-) and mCd59 ab(-/-)/Apoe(-/-) mice. CR2-Crry treatment also resulted in significantly reduced C3 and MAC deposition in the vasculature of both mice, as well as a significant reduction in the number of infiltrating macrophages and T cells.
Conclusion:
The data demonstrate the therapeutic potential of targeted complement inhibition.
Insights
Targeted complement inhibition using CR2-Crry effectively reduced atherosclerosis progression and lesion severity in mice. This approach offers a promising therapeutic strategy for preventing and treating this chronic inflammatory vascular disease.
Area of Science:
- Vascular Biology
- Immunology
- Pharmacology
Background:
- Atherosclerosis is a chronic inflammatory vascular disease.
- Complement activation products, including the membrane attack complex (MAC), play a role in atherogenesis.
- Targeting complement activation may offer a therapeutic strategy.
Purpose of the Study:
- Investigate the therapeutic potential of complement inhibition for atherosclerosis.
- Utilize CR2-Crry, a complement inhibitor targeting C3 activation sites, in a mouse model.
- Assess the efficacy of CR2-Crry in preventing and treating atherosclerosis.
Main Methods:
- Administered CR2-Crry to Apoe-deficient mice (both CD59 sufficient and deficient) on a high-fat diet.
- Quantified atherosclerotic lesions in the aorta and aortic root.
- Measured C3 and MAC deposition, and infiltration of macrophages and T cells.
Main Results:
- CR2-Crry treatment significantly reduced atherosclerotic lesions compared to controls.
- Inhibited accelerated atherogenesis observed in CD59-deficient mice.
- Decreased C3 and MAC deposition, and reduced inflammatory cell infiltration in the vasculature.
Conclusions:
- Targeted complement inhibition with CR2-Crry demonstrates therapeutic potential for atherosclerosis.
- CR2-Crry effectively reduces lesion development and associated inflammatory markers.
- This strategy warrants further investigation for clinical application in treating atherosclerosis.
