The effect of doxycycline on atherogenesis in apoE-knockout mice

Area of Science:

• Cardiovascular Research
• Pharmacology
• Biochemistry

Background:

• Matrix metalloproteinases (MMPs) play a role in atherosclerosis.
• Doxycycline is a clinically available MMP inhibitor at subantimicrobial doses.
• Apolipoprotein E (apoE)-knockout mice are a model for studying atherosclerosis.

Purpose of the Study:

• To investigate the effect of non-specific MMP inhibition by doxycycline on atherogenesis.
• To determine if doxycycline can ameliorate the development of atherosclerosis in apoE-knockout mice.

Main Methods:

• ApoE-knockout mice were treated with doxycycline (1.5 mg/kg b.w./day) orally.
• Atherogenesis was assessed using "en face" and "cross-section" methods.
• In-situ zymography was performed to evaluate gelatinase activity.

Main Results:

• Doxycycline treatment significantly attenuated atherogenesis compared to controls.
• "En face" analysis showed reduced lesion area (10.25±1.7% vs. 15.7±2.0%, p<0.05).
• "Cross-section" analysis revealed smaller lesion areas (66,254±7,468 μm(2) vs. 90,687±8,521 μm(2), p<0.05).
• In-situ zymography demonstrated decreased non-specific gelatinase activity in doxycycline-treated mice.

Conclusions:

• Subantimicrobial doxycycline effectively reduces atherogenesis in apoE-knockout mice.
• This study provides the first evidence of doxycycline's anti-atherogenic effects in this mouse model.
• MMP inhibition by doxycycline may be a therapeutic strategy for atherosclerosis.