Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

Djurić, Tamara; Stojković, Ljiljana; Živković, Maja; Končar, Igor; Stanković, Aleksandra; Djordjevic, A.; Alavantić, Dragan

doi:10.1016/j.clinbiochem.2012.05.032

Cited by 19 publications

(12 citation statements)

References 26 publications

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“…Although MMP-1 colocalizes with MMP-13 in the shoulder regions of inflamed human atheromatous plaques and that specific MMP-1 haplotypes associate with plaque burden, its direct role in atherosclerosis remains unclear. 7, 31–33 Macrophage-specific transgenic mice expressing human MMP-1 had less advanced atherosclerosis, but overexpression of human tissue inhibitor of metalloproteinase-1 (TIMP-1, an inhibitor of collagenases and other MMPs) showed a tendency to reduce atherosclerotic lesions in apoE −/− mice. 34 …”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-13 Predominates Over Matrix Metalloproteinase-8 as the Functional Interstitial Collagenase in Mouse Atheromata

Quillard

Araújo

Franck

et al. 2014

ATVB

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Objective Substantial evidence implicates interstitial collagenases of the MMP family in plaque rupture and fatal thrombosis. Understanding the compensatory mechanisms that may influence the expression of these enzymes and their functions therefore have important clinical implications. This study assessed in mice the unknown relative impact of the two principal collagenases on collagen content and other plaque characteristics. Approach and Results apoE−/− mice, MMP-13−/− apoE−/−, MMP-8−/− apoE−/− double knockout (DKO) mice, and MMP-13−/− MMP-8−/− apoE−/− triple knockout (TKO) mice consumed a high-cholesterol diet for 10 and 24 weeks. Both DKO and TKO mice showed comparable atherosclerotic lesion formation compared to apoE−/− controls. Analysis of aortic root sections indicated that lesions of MMP-8/MMP-13-deficient and MMP-13-deficient mice accumulate more fibrillar collagen than apoE−/− controls and MMP-8−/− apoE−/− DKO. We further tested the relative impact of MMPs on plaque collagenolysis using in situ zymography. MMP-13 deletion alone abrogated collagenolytic activity in lesions, indicating a predominant role for MMP-13 in this process. MMP-13 and MMP-13/MMP-8 deficiency did not alter macrophage content, but associated with reduced accumulation of smooth-muscle cells. Conclusions These results show that among MMP interstitial collagenases in mice, MMP-13 prevails over MMP-8 in collagen degradation in atheromata. These findings provide a rationale for the identification and selective targeting a predominant collagenase for modulating key aspects of plaque structure considered critical in clinical complications, although they do not translate directly to human lesions, which also contain MMP-1.

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-13 Predominates Over Matrix Metalloproteinase-8 as the Functional Interstitial Collagenase in Mouse Atheromata

Quillard

Araújo

Franck

et al. 2014

ATVB

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“…Among these variants, one of the most studied is the 1G>2G polymorphism in the promoter region of the gene, for the insertion allele confers greater transcriptional activity 14 which can have effects on the cell and therefore in the body. Thus, a significantly increased risk of atherosclerosis in the carotid artery in individuals carrying the 2G allele 15 and a greater presence of this allele in patients who had suffered ischemic stroke was observed 16 . However, until now associations of this polymorphism and calcific aortic valve disease had not been described, although the MMPs have been known to play an important role in their physiopathology 17,18 .…”

Section: Discussionmentioning

confidence: 97%

Asociación del polimorfismo 1G>2G de la MMP1 con calcificación de la válvula aórtica

Solache-Berrocal

Barral

Martı́n

et al. 2016

Rev Osteoporos Metab Miner

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Introduction: The most common cause of aortic stenosis is active calcium accumulation in the valve cusps, which implies serious clinical consequences. Various extracellular matrix metalloproteases (MMPs) have been implicated in the development of this disease. Therefore, the possible association between a functional MMP1 polymorphism and the amount of calcium deposited on the aortic valve is studied. Patients and methods: 45 patients undergoing valve replacement were included in the study. The calcium content in valve cusps removed during surgery was determined by computed micro-tomography. DNA was extracted from peripheral blood samples for genotyping the-1607 1G>2G polymorphism of MMP1 by PCR and subsequent digestion. Results: Significant differences were observed in the calcium content in aortic valves in individuals with different-1607 1G>2G genotypes (p=0.042). Thus, 2G allele carriers (homozygous or heterozygous) present higher calcium levels measured as BMD (p=0.004) as well as BV/TV (p=0.002). The association with BV/TV was independent of sex, age, degree of renal function and anatomy of the valve (p=0.02). BMD tendency (p=0.07) was also observed. Conclusion: The association between 1G>2G MMP1 polymorphism and calcium content of the aortic valve suggests that the 1G allele would have a protective effect against calcium deposits. These results support the importance of further study to confirm whether this polymorphism could be used as a possible predictor of aortic stenosis development.

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“…PAPP-A belongs to the metzincin superfamily of metalloproteinases [ 2 ] and is the founding member of a new metzincin subfamily, which differs from the four existing subfamilies (matrix metalloproteases, astacins, adamalysins/reprolysins, and serralysins) [ 15 ]. Djurić et al [ 27 ] found that the MMP-1 − 1062 G/2G polymorphism and specific haplotypes of three other promoter polymorphisms were significantly and independently associated with the occurrence of carotid plaques, while Li et al [ 28 ] reported that the inter-individual variability in MMP-12 variation may not be a risk factor for carotid plaques in the Chinese Han population.…”

Section: Discussionmentioning

confidence: 99%

Correlation of single nucleotide polymorphisms in the pregnancy-associated plasma protein-A gene with carotid plaques

Zhou

Cui

Yin

et al. 2015

BMC Cardiovasc Disord

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BackgroundPregnancy-associated plasma protein A (PAPP-A) is abundantly expressed in carotid plaques. This study investigated the association between single nucleotide polymorphisms (SNPs) of PAPP-A and the presence of carotid plaques.MethodsA total of 408 patients with carotid plaques and 493 controls were included in the study. All subjects were Southern Chinese Han. Carotid plaques were analyzed by computer tomography angiography. PAPP-A SNPs were identified by ligase detection reaction-polymerase chain reaction analysis. The PAPP-A genotypes rs3747823, rs7020782, and rs13290387 were analyzed.ResultsThe rs7020782 C allele genotype correlated with an increased risk of developing carotid plaques under the dominant, recessive, and additive models (adjusted odds ratios: 2.60, 2.36, and 3.48, respectively; P ≤ 0.001). Only C allele-carrying genotypes correlated with a significantly increased risk of carotid plaque based on studies stratified by age and sex under the dominant model. rs7020782 remained significantly associated with the risk of carotid plaque calcification after adjusting for age and potential confounders (adjusted odds ratio, 1.89; 95 % confidence interval, 1.17–3.08; P = 0.010).ConclusionsThis study found, for the first time, that the A˃C variation of rs7020782 might be an independent risk factor for carotid plaque development and calcification. The determination of such genotypes could provide a new tool for identifying individuals at high risk for carotid atherosclerosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-015-0041-1) contains supplementary material, which is available to authorized users.

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Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

Cited by 19 publications

References 26 publications

Matrix Metalloproteinase-13 Predominates Over Matrix Metalloproteinase-8 as the Functional Interstitial Collagenase in Mouse Atheromata

Matrix Metalloproteinase-13 Predominates Over Matrix Metalloproteinase-8 as the Functional Interstitial Collagenase in Mouse Atheromata

Asociación del polimorfismo 1G>2G de la MMP1 con calcificación de la válvula aórtica

Correlation of single nucleotide polymorphisms in the pregnancy-associated plasma protein-A gene with carotid plaques

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