Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice

Area of Science:

• Cardiovascular Research
• Gene Therapy
• Proteoglycan Biology

Background:

• Atherosclerosis involves macrophage and extracellular matrix accumulation in arteries.
• Decorin, a proteoglycan, influences cell behavior and growth factor activity.
• Apolipoprotein E-deficient (ApoE(-/-)) mice are a model for studying atherosclerosis.

Purpose of the Study:

• To investigate the impact of decorin overexpression on atherosclerosis progression in ApoE(-/-) mice.
• To evaluate decorin's therapeutic potential in a mouse model of atherosclerosis.

Main Methods:

• Adenovirus-mediated delivery of the human decorin gene (Ad-Dcn) or a control (LacZ) via intravenous injection.
• Treatment administered at two time points: early (10 weeks) and delayed (20 weeks) in ApoE(-/-) mice.
• Assessment of aortic root lesion size, macrophage content, gelatinase activity, collagen content, plasma triglycerides, and TGF-beta1 levels.

Main Results:

• Systemic decorin overexpression significantly reduced atherosclerotic lesion size in both early and delayed treatment groups compared to controls.
• Ad-Dcn treatment led to decreased macrophage infiltration, gelatinase activity, and collagen content within plaques.
• Plasma triglyceride levels were reduced, and decorin formed complexes with TGF-beta1, lowering free TGF-beta1.

Conclusions:

• Systemic decorin overexpression effectively slows atherosclerosis progression in ApoE(-/-) mice.
• Decorin reduces key pathological features of atherosclerosis including inflammation, lipid accumulation, and fibrosis.
• Decorin's mechanism involves modulating TGF-beta1 activity and improving lipid profiles.