Article

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

University of Texas Health Science Center School of Public Health, Human Genetics Center, 1200 Hermann Pressler, Houston, TX 77030, United States.
Atherosclerosis (Impact Factor: 3.97). 05/2010; 210(1):188-93. DOI: 10.1016/j.atherosclerosis.2009.12.006
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
66 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we investigated the effects of apolipoprotein A-I (apoA-I) on matrix metalloproteinase-2 (MMP-2) expression in vivo and in vitro. First, we detected the effects of apoA-I on aorta MMP-2, peroxisome proliferator-activated receptor α/γ (PPAR α/γ), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) expressions in atherosclerotic rabbit models using immunohistochemical methods. The results showed that the expressions of MMP-2, COX-2, and NF-κB were decreased in aortas of atherosclerotic rabbits treated with apoA-I, while PPAR α/γ expression was increased. Then, we chose the important inflammation cells, macrophages to testify those effects in vitro. Macrophages were divided into six groups and treated with different concentrations of apoA-I, the mRNA expressions of MMP-2, PPAR α/γ, and COX-2 were then determined using reverse-transcription polymerase chain reaction, and protein expression of PPAR γ, NF-κB were detected by western blot analysis. The levels of MMP-2 and PPAR α in cultured supernatants were determined using enzyme-linked immunosorbent assays. Interestingly, the in vitro results were similar to the results of the in vivo study. After incubation with apoA-I for 24 h, the expressions of MMP-2, COX-2, and NF-κB were decreased, while PPAR α/γ expression was increased. In consideration of their particular roles in the process of making plaque stable in vivo and in vitro, we speculate that the inhibitory effect of apoA-I on MMP-2 expression may have a close relationship with the effects of apoA-I on PPAR α/γ, COX-2, and NF-κB expressions. Although further research is needed to clarify the underlying mechanisms of these effects, our findings provide a novel insight into the anti-atherosclerotic plaque rupture effects of apoA-I.
    Acta Biochimica et Biophysica Sinica 01/2013; 45(3). DOI:10.1093/abbs/gms121 · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Matrix metalloproteinases (MMPs) and their inhibitors essentially contribute to a variety of pathophysiologies by modulating cell migration, tissue degradation and inflammation. Platelet-associated MMP activity appears to play a major role in these processes. First, platelets can concentrate leukocyte-derived MMP activity to sites of vascular injury by leukocyte recruitment. Second, platelets stimulate MMP production in e.g. leukocytes, endothelial cells, or tumour cells by direct receptor interaction or/and by paracrine pathways. Third, platelets synthesise and secrete a variety of MMPs including MMP-1, MMP-2, MMP-3, and MMP-14 (MT1-MMP), and potentially MMP-9 as well as the tissue inhibitors of metalloproteinase (TIMPs). This review focuses on platelet-derived and platelet-induced MMPs and their inhibitors.
    Thrombosis and Haemostasis 07/2013; 110(4). DOI:10.1160/TH13-02-0113 · 5.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is no doubt that the functional and structural integrity of the endothelium is critical in maintaining vascular homoeostasis and in preventing atherosclerosis. In the light of epidemiological and experimental studies, magnesium deficiency is emerging as an inducer of endothelial dysfunction. In particular, data on the effects of low extracellular magnesium on cultured endothelial cells reinforce the idea that correcting magnesium homoeostasis might be a helpful and inexpensive intervention to prevent and treat endothelial dysfunction and, consequently, atherosclerosis.
    Clinical Science 05/2012; 122(9):397-407. DOI:10.1042/CS20110506 · 5.63 Impact Factor

Preview

Download
0 Downloads
Available from