Effect of minocycline on carotid atherosclerotic plaques

Abstract

Objectives: To investigate whether minocycline could attenuate the expression of extracellular matrix metalloproteinase inducer (CD147) and matrix metalloproteinase (MMP)-9 and enhance stability of atherosclerotic plaques.

Methods: Twenty-four New Zealand rabbits underwent balloon-induced endothelial injury of right carotid artery and were fed 1% cholesterol diet for 16 weeks. From week 12 to week 16, the animals were intervened with minocycline (2·5 mg kg⁻¹ d⁻¹, group A), atorvastatin (2·5 mg kg⁻¹ d⁻¹, group B) or were not treated with drugs (group C). After 16 weeks, all the rabbits were sacrificed by Chinese Russell’s viper venom and histamine injection, then serum and right common carotid arteries were collected for biochemical, histological, and reverse transcription polymerase chain reaction (RT-PCR) analysis.

Results: A rabbit model of atherosclerotic vulnerable plaques was established. Minocycline significantly increased the thickness of the plaque fibrous caps and decreased the positive staining area of macrophages in group A. When compared with group C, CD147, and MMP-9 expression in both mRNA and protein level were remarkably reduced in group A and B (P < 0·05). However, there was no significant difference between group A and B. Serum TC and low-density lipoprotein cholesterol (LDL-C) levels were decreased in the Atorvastatin group (P < 0·05), while minocycline had no obvious influence on the serum lipid levels. The incidence of plaque ruptures in group A (14·3%) and group B (14·3%) was lower than that in group C (66·7%, P < 0·05).

Conclusions: Minocycline intervention significantly reduced the activity of CD147, MMP in plaque and histologically enhanced plaque stabilization. Minocycline was equally effective as Atorvastatin.

Keywords:

• Atherosclerosis
• Plaque
• CD147
• MMP-9
• Minocycline