MMP2 genetic variation is associated with measures of fibrous cap thickness: The Atherosclerosis Risk in Communities Carotid MRI Study

ArticleinAtherosclerosis 210(1):188-93 · May 2010with5 Reads
DOI: 10.1016/j.atherosclerosis.2009.12.006 · Source: PubMed
Genetic variation in matrix metalloproteinase (MMP) promoter regions alter the transcriptional activity of MMPs and has been consistently associated with CHD, presumably through plaque degradation and remodeling. We examined the association of MMP promoter variation with multiple plaque characteristics measured by gadolinium-enhanced MRI among 1700 participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. For the analyses presented here, 1700 participants of the biracial ARIC Carotid MRI Study ( approximately 1000 participants with thick carotid artery walls and approximately 700 randomly sampled participants) were evaluated for associations of MMP genetic variation with multiple plaque characteristics, including carotid artery wall thickness, lipid core and fibrous cap measures. MRI studies were performed on a 1.5T scanner equipped with a bilateral 4-element phased array carotid coil. Fifty-one percent of the participants were female, 77% white, 23% African American, and the mean age was 70 years. MMP2 C-1306T variant genotypes (CT+TT) were significantly associated with higher cap thickness measures, but not with wall thickness or lipid core measures. Individuals with the CC genotype had approximately 0.1mm thinner cap thickness compared to those carrying a T allele (P=0.02). Genetic variation within the MMP2 promoter region was associated with cap thickness and therefore may influence the role of MMP2 in plaque vulnerability.
    • "The gelatinases MMP2 and MMP9 have been frequently associated with vascular remodeling processes in atherosclerosis (Back et al., 2010), and MMP2 has been suggested to play an important role in remodeling of the ECM and the vascular wall of lung vessels in pulmonary hypertension (Hassoun, 2005; Lepetit et al., 2005; Raffetto and Khalil, 2008). Increased MMP2 expression due to polymorphisms in the MMP2 promoter seems to be relevant for the risk of cardiovascular events (Volcik et al., 2010). The regulatory pathways underlying the expression of MMP2 in the vasculature, however, are not completely resolved. "
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    • "Indeed, an increased expression of MMPs in human atherosclerotic plaques and, in particular, a marked upregulation of MMP-9 in unstable carotid plaque have been demonstrated [32]. Recently, genetic variation within the MMP-2 promoter region was associated with cap thickness and therefore it may influence the role of MMP-2 in plaque vulnerability [33]. "
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