Carotid plaque vulnerability and matrix metalloproteinase -1 and -9 genetic polymorphisms

Aim. Matrix metalloproteinase 1 (MMP-1) and 9 (MMP-9) are alleged to influence atherosclerotic plaques evolution, vulnerability (tendency to rupture), and development of vascular events. MMPs expression depends on environmental stimuli and functional (i.e. determining differential gene expression) genetic polymorphisms (PM). This study evaluates the relationship between MMP PM and carotid plaque features of vulnerability. Methods. Histopathological traits of plaque instability (plaque and lipid core size, fibrous cap thickness, erosion, thrombosis, macrophages, smooth muscle cells [SMC], and elastic fibers content) have been determined in 31 carotid plaques obtained from thromboendarterectomy and then compared according to a genetic MMP-1 PM (rs1799750, G insertion/deletion at -1607) and MMP-9 PM (rs3222264, CA microsatellite around -90) of the carrier patients. Results. Carriers of MMP-1 G insertion have, on average, a smaller plaque and a thicker fibrous cap (standardized by plaque size) with higher SMC and elastic fibers content. Carriers of more than 21 repeats in MMP-9 microsatellite have plaques with larger lipid core. Conclusions. In carotid plaques, a MMP-1 genetic variant accounting for higher expression is associated with histopathology signs of less vulnerable plaques, while MMP-9 genotypes increasing expression are associated with a trait of plaque vulnerability. MMP-1 and MMP-9 can have an opposite role, protective for the former, causative for the latter, in determining atherosclerotic plaque evolution.