Abstract P279: Circulating Levels of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Matrix Metalloproteinase-2 (MMP-2) in Relation to Cardiovascular Risk Factors and Subclinical and Clinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA) Study
Atherosclerosis arises from an accumulation of plaque and can develop from an imbalance of proteins that regulate the extracellular matrix (ECM). Matrix metalloproteinases (MMP) are gelatinases that degrade collagen and are regulated by tissue inhibitors of metalloproteinases (TIMPs). MMP-2 is thought to play a role in proliferation, vascular remodeling, and oxidized LDL induced smooth muscle migration. Using a race/ethnic stratified random sample of 2,403 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) at Exam 2, we investigated the association of soluble serum MMP-2 and TIMP-2 with traditional risk factors and subclinical and clinical cardiovascular disease (CVD). Regression methods were used to assess the relationship of protein and risk factor levels with adjustment for age and sex. The Tobit model was used for coronary artery calcium (CAC), and Cox proportional hazards regression for incident CVD events (myocardial infarction, stroke, angina, or other atherosclerotic death) with an average follow-up time of 7.3 years. All analyses were stratified by race/ethnicity. Mean levels of MMP-2 and TIMP-2 differed significantly by race/ethnicity (Table 1) and the two proteins were significantly correlated to each other (r = 0.72, 0.84, 0.81, 0.76 for Caucasian, Chinese, African, and Hispanic Americans respectively). Both proteins were positively associated with HDL cholesterol in Caucasian, Chinese, and African but not Hispanic Americans (interaction p = 0.01 for MMP-2 and 0.003 for TIMP-2). An inverse association of MMP-2 and LDL was observed only in Chinese Americans (interaction p = 0.03). There were no significant associations with subclinical or clinical disease for individual protein levels in any of the ethnic groups studied, albeit power was limited, given the few events in the subset understudy. We have shown in this large cohort that mean circulating MMP-2 and TIMP-2 levels differed by ethnicity and that significant differences in protein associations and CVD risk factors were observed.
- © 2013 by American Heart Association, Inc.