MMP-3 (5A/6A) Polymorphism Does Not Influence Human Smooth Muscle Cell Invasion

Maqbool, Azhar; Keswani, Anita; Galloway, S; O’Regan, David; Ball, Stephen G.; Turner, Neil A.; Porter, Karen E.

doi:10.1016/j.jss.2011.03.043

Cited by 3 publications

(4 citation statements)

References 40 publications

(51 reference statements)

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“…Some authors reported higher plasma levels of MMP‐3 associated with the 6A allele of the MMP‐3(‐1612 5A/6A) SNP in patients with coronary artery disease and healthy controls of Swedish and Indian extraction . Other authors did not find differences among the diverse genotypes in the MMP‐3 expression of vascular smooth muscle cells of English patients undergoing coronary artery bypass surgery , or even an apparently enhancing effect of the 5A allele in MMP‐3 expression of fibroblasts and vascular smooth muscle cells . Finally, an Iranian study found higher MMP‐3 plasma levels associated with the 6A allele, compared with the 5A allele, of the MMP‐3(‐1171 5A/6A) SNP in healthy individuals, but the opposite pattern was observed in patients with acute myocardial infarction .…”

Section: Discussionmentioning

confidence: 97%

“…However, some in vivo studies have found, surprisingly, that carriers of the 6A allele of this MMP‐3 SNP had higher plasma MMP‐3 levels than those with the 5A allele in patients with coronary disease and also in healthy populations . No MMP‐3 plasma levels differences among MMP‐3 (‐1612 5A/6A) SNP genotype carriers were observed by others, however . MMP‐3 (‐1612 5A/6A) SNP has been associated with coronary disease, vascular aneurysms, brain stroke, cancer and arthritis, but not so far with infections .…”

Section: Introductionmentioning

confidence: 86%

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The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions

Collazos

Asensi

Martin

et al. 2015

Clinical and Experimental Immunology

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SummaryMatrix metalloproteases (MMPs) are increased in different infections due to their role in controlling immune responses and are regulated by tissue inhibitors (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce changes in MMP genes, mRNA and protein expression. Gender might also modify MMP plasma levels. In order to determine the weight of these variables on MMP secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV-hepatitis C virus (HCV) co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP-1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(-77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had higher levels than allele 5A carriers, an effect that was magnified by sepsis. Independent predictors of higher MMP-3 levels were male gender (P 5 0Á0001), MMP-3 (-1612 5A/6A) SNP (P 5 0Á001), higher levels of TIMP-4 (P 5 0Á004) and MMP-8 (P 5 0Á006) and lower levels of MMP-1 (P 5 0Á03) by multivariate analysis. No strong associations with gender or SNPs were observed for other MMPs or TIMPs. In conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3 plasma levels significantly, especially in patients with severe bacterial sepsis. This confounding gender effect needs to be addressed when evaluating MMP-3 plasma levels in any infectious or non-infectious condition.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 86%

The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions

Collazos

Asensi

Martin

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

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“…The method for studying invasion of human aortic smooth muscle cells through extracellular matrix using a matrigel-coated transwell system (BD Biosciences, San Jose, CA) was similar to that described by Maqbool et al (2012). Briefly, human aortic smooth muscle cells (5 × 10 4 ; Invitrogen, Grand Island, NY) were loaded onto the matrigel-coated membrane in the upper chamber of the transwell system, and allowed to invade through the matrigel to the bottom side of the membrane for 24 hrs.…”

Section: Methodsmentioning

confidence: 99%

Nicotinic acetylcholine receptor mediates nicotine-induced actin cytoskeletal remodeling and extracellular matrix degradation by vascular smooth muscle cells

Gu¹,

Fonseca²,

Hai³

2013

Vascular Pharmacology

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Cigarette smoking is a significant risk factor for atherosclerosis, which involves the invasion of vascular smooth muscle cells (VSMCs) from the media to intima. A hallmark of many invasive cells is actin cytoskeletal remodeling in the form of podosomes, accompanied by extracellular matrix (ECM) degradation. A7r5 VSMCs form podosomes in response to PKC activation. In this study, we found that cigarette smoke extract, nicotine, and the cholinergic agonist, carbachol, were similarly effective in inducing the formation of podosome rosettes in A7r5 VSMCs. α-Bungarotoxin and atropine experiments confirmed the involvement of nicotinic acetylcholine receptors (nAChRs). Western blotting and immunofluorescence experiments revealed the aggregation of nAChRs at podosome rosettes. Cycloheximide experiments and media exchange experiments suggested that autocrine factor(s) and intracellular phenotypic modulation are putative mechanisms. In situ zymography experiments indicated that, in response to PKC activation, nicotine-treated cells degraded ECM near podosome rosettes, and possibly endocytose ECM fragments to intracellular compartments. Invasion assay of human aortic smooth muscle cells indicated that nicotine and PKC activation individually and synergistically enhanced cell invasion through ECM. Results from this study suggest that nicotine enhances the ability of VSMCs to degrade and invade ECM. nAChR activation, actin cytoskeletal remodeling and phenotypic modulation are possible mechanisms.

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“…There is evidence suggesting that 5A/6A polymorphism is related to MMP-3 expression and activation and individuals' susceptibility to many cardiovascular diseases [120]. However, MMP-3 5A/6A polymorphism does not affect invasion of saphenous vein SMCs isolated from patients with different genotypes [121]. …”

Section: Mmps and Vsmc Behaviorsmentioning

confidence: 99%

Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

Chen

Jin

Yang

et al. 2013

Mediators of Inflammation

384

307

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Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) and its interaction with extracellular matrix (ECM) play a critical role in the processes. Matrix metalloproteinases (MMPs), well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential.

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MMP-3 (5A/6A) Polymorphism Does Not Influence Human Smooth Muscle Cell Invasion

Cited by 3 publications

References 40 publications

The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions

The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions

Nicotinic acetylcholine receptor mediates nicotine-induced actin cytoskeletal remodeling and extracellular matrix degradation by vascular smooth muscle cells

Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

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