Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE(- forward slash -) and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE(- forward slash -) and ovariectomized mice (OVX). Female ApoE(- forward slash -)-knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE(- forward slash -)/OVX vehicle and ApoE(- forward slash -)/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE(- forward slash -)/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE(- forward slash -)/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE(- forward slash -)/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.