Increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition is associated with increased nuclear factor-κB and activator protein-1 activity

Knipp, Brian S.; Ailawadi, Gorav; Ford, John W.; Peterson, David A.; Eagleton, Matthew J.; Roelofs, Karen J.; Hannawa, Kevin K.; Deogracias, Michael P.; Ji, Baoan; Logsdon, Craig D.; Graziano, Kathleen; Simeone, Diane M.; Thompson, Robert W.; Henke, Peter K.; Stanley, James C.; Upchurch, Gilbert R.

doi:10.1016/s0022-4804(03)00306-8

Cited by 41 publications

(33 citation statements)

References 33 publications

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“…Indeed, the potential for regulation of MMP-9 expression and activation by NOS2-derived NO has received considerable interest in previous studies (22,23). Although several studies have suggested that NO inhibits cytokine-mediated MMP-9 expression in mesangial cells or vascular smooth muscle cells (22,24), others have reported contrasting observations in vascular smooth muscle cells and chrondocytes (25). We have previously demonstrated that cytokine-induced MMP-9 expression in tracheobronchial epithelial cells is suppressed by exogenous high concentrations of NO and S-nitrosothiols (26), but it is unclear whether this is relevant to MMP-9 regulation by endogenous NOS activity under normal physiologic conditions.…”

Section: Clinical Relevancementioning

confidence: 99%

Nitric Oxide Promotes Airway Epithelial Wound Repair through Enhanced Activation of MMP-9

Bove

Wesley

Greul

et al. 2007

Am J Respir Cell Mol Biol

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The airway epithelium provides a protective barrier against inhaled environmental toxins and microorganisms, and epithelial injury initiates a number of processes to restore its barrier integrity, including activation of matrix metalloproteinases such as MMP-9 (92-kD gelatinase B). Airway epithelial cells continuously produce nitric oxide (NO), which has been linked to cell migration and MMP-9 regulation in several cell types, but the importance of epithelial NO in mediating airway epithelial repair or MMP-9 activation is unknown. Using primary or immortalized human bronchial epithelial cells, we demonstrate that low concentrations of NO promote epithelial cell migration and wound repair in an in vitro wound assay, which was associated with increased localized expression and activation of MMP-9. In addition, in HBE1 cells that were stably transfected with inducible NOS (NOS2), to mimic constitutive epithelial NOS2 expression in vivo, NOS inhibition decreased epithelial wound repair and MMP-9 expression. The stimulatory effects of NO on epithelial wound repair and MMP-9 expression were dependent on cGMPmediated pathways and were inhibited by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase. Inhibition of cGMP-dependent protein kinase (PKG) attenuated NO-mediated epithelial wound closure, but did not affect MMP-9 expression. However, pharmacologic MMP inhibition and siRNA knockdown of MMP-9 expression demonstrated the contribution of MMP-9 to NO-mediated wound closure. Overall, our results demonstrate that NOS2-derived NO contributes to airway epithelial repair by both PKG-dependent and -independent mechanisms, and involves NO-dependent expression and activation of MMP-9.

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Section: Clinical Relevancementioning

confidence: 99%

Nitric Oxide Promotes Airway Epithelial Wound Repair through Enhanced Activation of MMP-9

Bove

Wesley

Greul

et al. 2007

Am J Respir Cell Mol Biol

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“…iNOS produces NO in large quantities, is stimulated by vascular damage, and abrogates the vascular protective effects of eNOS-produced NO. NO produced by iNOS thereby promotes injury-induced vasospasm, adherence and aggregation of platelets to the injury site, transvessel migration of SMCs and inflammatory cells (2,9,12,26,38,52), and upregulation of MMP expression (26). MMP expression leads to the enzymatic degradation of the ECM and facilitates SMC migration through the media and IEL of the injured vessel.…”

Section: Discussionmentioning

confidence: 99%

Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty

Nestor

Cicila

Karol

et al. 2006

Physiological Genomics

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age analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty. Physiol Genomics 25: 286 -293, 2006. First published January 24, 2006 doi: 10.1152/physiolgenomics.00135.2005.-Neointimal hyperplasia (NIH), a result of vascular injury, is due to the migration and proliferation of smooth muscle cells through the media and internal elastic lamina leading to vascular occlusion. We used a rat model to find the genetic regions controlling NIH after endothelial denudation in two divergent inbred strains of rats. The Brown Norway (BN) and spontaneously hypertensive rat (SHR) strains have a 2.5-fold difference in injury-induced NIH. A population of 301 F2 (SHR ϫ BN) rats underwent a standard vascular injury followed by phenotyping 8 wk after injury to identify quantitative trait loci (QTL) responsible for this strain difference. Interval mapping identified two %NIH QTL on rat chromosomes 3 and 6 [logarithm of odds (LOD) scores 2.5, 2.2] and QTL for other injured vascular wall changes on rat chromosomes 3, 4, and 15 (LOD scores 2.0 -4.6). Also, QTL for control vessel media width (MW) and media area (MA) were found on chromosome 6 with LOD scores of 2.3 and 2.5, suggesting that linkage exists between these control vessel parameters and NIH production. These results represent the first genetic analysis for the identification of NIH QTL and QTL associated with the vascular injury response.quantitative trait loci; restenosis; vascular injury; inbred strains; Brown Norway rat; spontaneously hypertensive rat INTERVENTIONS IN THE CARDIOVASCULAR system such as arterial grafts, stents, and balloon angioplasties often fail because of the development of neointimal hyperplasia (NIH). There are no effective therapies to prevent or treat this complication. For example, restenosis secondary to NIH occurs in 30 -40% of patients after balloon angioplasty for coronary artery disease (27). Drug-eluting stents reduce the occurrence of short-term NIH to 20 -30%, but the long-term efficacy of these devices is not known (27). NIH is also associated with the development of significant restenosis in 20% of patients undergoing carotid endarterectomy (1) and is a major contributor to graft failure in coronary and peripheral arteries (24).NIH is triggered by vascular endothelial cell (VEC) disruption and injury that leads to smooth muscle cell (SMC) migration to subendothelial injury sites, followed by SMC proliferation and apoptosis. Significant neointimal thickening and decreased lumen areas are seen within 2 wk after vascular injury (16, 32). However, vascular occlusion can continue after 2 wk as SMC size increases (16, 32) and proteoglycan matrix deposits continue to thicken the neointima (8,28,36,37,45). Many factors are involved in, and possibly responsible for, genetically determined variations in the NIH injury response between different strains of animals and among individual patients (1). We postulate that heritable variations in the genes for these vascular injury response elements are possible candidate...

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“…(77) In contrast, NO production from RA-SMCs (via iNOS induced by LPS and IFN-g) had a positive effect on MMP-9 expression, increasing its mRNA by >10-fold; the sGC inhibitor ODQ (1H- [1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one) blocked this effect. (78) NO was shown to induce glutamate release from vertebrate photoreceptor synapses by activating cGMP/cyclic nucleotidegated (CNG) cation channels.…”

Section: Secretionmentioning

confidence: 95%

Nitric oxide and metastatic cell behaviour

Williams

Djamgoz

2005

BioEssays

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Nitric oxide (NO) is a pleiotropic signalling molecule that subserves a wide variety of basic cellular functions and also manifests itself pathophysiologically. As regards cancer and its progression, however, the reported role of NO appears surprisingly inconsistent. In this review, we focus on metastasis, the process of cancer cell spread and secondary tumour formation. In a 'reductionist' approach, we consider the metastatic cascade to be made up of a series of basic cellular behaviours (such as proliferation, apoptosis, adhesion, secretion migration, invasion and angiogenesis). We evaluate how NO controls such behaviours, in comparison with normal cells. The available information suggests strongly that NO signalling would be expected to regulate these behaviours both positively and negatively and this probably leads to the observed apparent variability in the NO status of cancer cells and tissues. Thus, the role of NO in cancer is more complex than previously thought. A number of suggestions are made, including consideration of novel mechanisms, such as ion channels, in order to achieve a more consistent and integrated understanding of NO signalling in cancer and to realise its clinical potential.

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Increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition is associated with increased nuclear factor-κB and activator protein-1 activity

Cited by 41 publications

References 33 publications

Nitric Oxide Promotes Airway Epithelial Wound Repair through Enhanced Activation of MMP-9

Nitric Oxide Promotes Airway Epithelial Wound Repair through Enhanced Activation of MMP-9

Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty

Nitric oxide and metastatic cell behaviour

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