Association of Circulating Matrix Metalloproteinases With Carotid Artery Characteristics

OBJECTIVE: To examine the relationship of plasma levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP-1) with carotid artery characteristics measured by MRI in a cross-sectional investigation among Atherosclerosis Risk in Communities Carotid MRI Study participants. METHODS AND RESULTS: A stratified random sample was recruited based on intima-media thickness from a previous ultrasonographic examination. A high-resolution gadolinium-enhanced MRI examination of the carotid artery was performed from 2004 to 2005 on 1901 Atherosclerosis Risk in Communities cohort participants. Multiple carotid wall characteristics, including wall thickness, lumen area, calcium area, lipid core, and fibrous cap measures, were evaluated for associations with plasma MMPs 1, 2, 3, 7, 8, and 9 and TIMP-1. Plasma MMPs 1, 3, and 7 were significantly higher among participants in the high intima-media thickness group compared with those in the low intima-media thickness group. The normalized wall index was independently associated with MMPs 3 and 7 and TIMP-1. MMP-7 was positively associated with carotid calcification. The mean fibrous cap thickness was significantly higher in individuals with elevated TIMP-1 levels. In addition, TIMP-1 was positively associated with measures of lipid core. CONCLUSION: Circulating levels of specific MMPs and TIMP-1 were associated with carotid wall remodeling and structural changes related to plaque burden in elderly participants.