MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis

Fiotti, Nicola; Altamura, Nicola; Fisicaro, Maurizio; Carraro, Nicola; Uxa, Laura; Grassi, Gabriele; Torelli, Lucio; Gobbato, Raffaella; Guarnieri, Gianfranco; Baxter, B. Timothy; Giansante, Carlo

doi:10.1161/01.atv.0000219233.31702.c9

Cited by 36 publications

(20 citation statements)

References 34 publications

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“…Recently, several lines of researches have showed that MMP-9 plays an important role in atherogenesis by promoting degradation of the extracellular matrix [18,19]. Within the vulnerable atheromatous plaques, particularly in the inflamed shoulder and fibrous caps, there exists strong MMP-9 expression [20].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Induces Inflammatory Response Partly Via Toll-Like Receptor 4-Dependent Signaling Pathway in Vascular Smooth Muscle Cells

Ji¹,

Liu²,

Wang

et al. 2009

Cell Physiol Biochem

132

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Angiotensin (Ang II) plays an important role in atherosclerosis through proinflammatory effect. Toll-like receptor 4 (TLR4) may mediate inflammatory response. It is unknown whether TLR4 mediates the proinflammatory effect of Ang II. Thus, we observed the role and signaling pathway of TLR4 in Ang II-induced inflammation in rat vascular smooth muscle cells (VSMCs). Ang II and LPS stimulated TNF-α secretion and inhibited 6-keto-PGF_1α production, upregulated MMP-9 and downregulated PPARγ and PPARαin rat VSMCs. Ang II also distinctly upregulated TLR4 expression in the cells. Pretreatment of the cells with anti-TLR4 antibody prior to Ang II stimulation significantly diminished the effects of Ang II. These suggest that Ang II stimulates VSMCs to produce inflammation through regulation of the proinflammatory and the antiinflammtory factors via TLR4-dependent mechanism. The further investigations showed that AT1 receptor antagonist losartan or ERK1/2 inhibitor PD098059 inhibited Ang II-induced TLR4 expression, TLR4 inhibitor prevented Ang II- induced IP-10 expression, anti-IP-10 antibody partly abolished Ang II- induced PKC increase, and PKC inhibitor chelerythrine suppressed Ang II- induced NF-κB expression. These demonstrate that TLR4-mediated proinflammatory effect of Ang II in VSMCs involves AT1/ERK1/2/TLR4/IP-10/ PKC/NF-κB pathway. Our results provide the evidence that Ang II induces inflammatory response involved in pathogenesis of atherosclerosis partly via TLR4- dependent signaling pathway in VSMCs.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Induces Inflammatory Response Partly Via Toll-Like Receptor 4-Dependent Signaling Pathway in Vascular Smooth Muscle Cells

Ji¹,

Liu²,

Wang

et al. 2009

Cell Physiol Biochem

132

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“…Genes encoding vascular adhesion molecules, matrix metalloproteinases (MMPs), and interleukins are all downstream targets of NF-κB. Genetic polymorphisms at the MCP-1 (17), MMP-3 (18,19), MMP-9 (20) and interleukin-6 (IL-6) (21) genes were found to be associated with carotid atherosclerosis. In our previous study (7), BRAP was found to be involved in the NF-κB-dependent inflammatory pathway.…”

mentioning

confidence: 99%

BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid Atherosclerosis

Liao

Wang

Guo

et al. 2011

Mol Med

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“…High genetic variability was observed (k = 13), even higher than that reported for African-American populations (k = 11) (Ferrand et al, 2002). This diversity was stronger in the Mestizo population, which exhibited the most frequent alleles of European (CA 14 ), Asian (CA 21 ), and African-American (CA >21 ) populations, as well as significant heterogeneity (6%, P ≤ 0.0001) (Ferrand et al, 2002;Fiotti et al, 2006;Lee et al, 2010). These findings were corroborated with PCA and genetic distance analyses, which showed relative proximity between the Mestizo population and their historical parental populations (Asian, European, and African) (Salazar-Flores et al, 2010).…”

Section: Discussionmentioning

confidence: 74%

“…Studies on the MMP-9 gene have associated the length of the dinucleotide repeat with promoter activity, suggesting that (CA) 14 may cause a significant decrease (up to 50%) in transcriptional activity in comparison to (CA) 21 (Shimajiri et al, 1999;Ferrand et al, 2002). Therefore, polymorphisms of the MMP-9 gene have been implicated in the susceptibility to various diseases such as cancer (Kader et al, 2006), lipid levels (Mazzotti et al, 2014), cardiovascular diseases (Fiotti et al, 2006), and Alzheimer's disease (Flex et al, 2013), among others.…”

Section: Introductionmentioning

confidence: 99%

Interethnic variation of the MMP-9 microsatellite in Amerindian and Mexican Mestizo populations: considerations for genetic association studies

Camacho-Mejorado¹,

Noris²,

Santana³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We studied the interethnic variation of the MMP-9 microsatellite in the Mestizo and Amerindian populations using R. Camacho-Mejorado et al. 2930©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 2929-2939 (2015) blood samples collected from 435 healthy unrelated individuals from the Central Valley of Mexico. DNA samples were genotyped using the -90 (CA) [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] repeat near the MMP transcriptional start site using capillary electrophoresis. Our data were compared with those from African, Asian, and European populations (N = 729). Both Mestizo and Amerindian populations were in Hardy-Weinberg equilibrium (P ≥ 0.05). However, strong genetic heterogeneity was found within the Mestizo population (94%, P ≤ 0.0001), which exhibited the highest frequency of Amerindian, African, and European alleles. Likewise, Amerindians showed 6.7% variation among populations (P ≤ 0.0001), suggesting a genetic substructure potentially associated with linguistic affiliations. These findings were corroborated with principal component and population differentiation analyses, which showed relative proximity among the Mestizos and their historical parental populations: Asian (F st ≥ 0.05), European (F st ≥ 0.09), and African (F st ≥ 0.02). Nevertheless, important differences were found between Mestizo and Nahuas (P ≤ 0.0001), and between Mestizo and Me'Phaas (P ≤ 0.0001). These findings highlight the importance of determining local-specific patterns to establish the population variability of MMP-9 and other polymorphic markers. Validation of candidate markers is critical to identifying risk factors; however, this depends on knowledge of population genetic variation, which increases the possibility of finding true causative variants. We also show that dissimilar ethnic backgrounds might lead to spurious associations. Our study provides useful considerations for greater accuracy and robustness in future genetic association studies.

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MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis

Abstract: The number of repeats (> or =22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

Cited by 36 publications

References 34 publications

Angiotensin II Induces Inflammatory Response Partly Via Toll-Like Receptor 4-Dependent Signaling Pathway in Vascular Smooth Muscle Cells

Angiotensin II Induces Inflammatory Response Partly Via Toll-Like Receptor 4-Dependent Signaling Pathway in Vascular Smooth Muscle Cells

BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid Atherosclerosis

Interethnic variation of the MMP-9 microsatellite in Amerindian and Mexican Mestizo populations: considerations for genetic association studies

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