Primate Smooth Muscle Cell Migration From Aortic Explants Is Mediated by Endogenous Platelet-Derived Growth Factor and Basic Fibroblast Growth Factor Acting Through Matrix Metalloproteinases 2 and 9

Kenagy, Richard D.; Hart, C. E.; Stetler-Stevenson, William G.; Clowes, A W

doi:10.1161/01.cir.96.10.3555

Cited by 136 publications

(116 citation statements)

References 62 publications

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“…4 -6 Among these proteases, MMPs and the serine protease system, plasminogen/plasmin, have been believed to contribute to matrix remodeling and to play an essential role in SMC migration. [7][8][9][10] This is supported by findings that MMPs and plasminogen activator levels are elevated after balloon injury to rat carotid arteries. 7,8,11 However, previous observations have suggested that the even effective inhibition of MMPs and serine proteases might not sufficiently arrest neointima formation.…”

mentioning

confidence: 63%

“…Extensive investigations regarding vascular remodeling have been performed using two proteolytic systems, the fibrinolytic (plasminogen/plasmin) and the MMP systems. [7][8][9][10] Abundant evidence now supports a potential role for these two proteolytic systems in vascular remodeling. 7,8,11 However, recent studies using mice with targeted gene deletion and inhibitors of these proteases have suggested that other proteolytic Both cathepsin S and K protein levels in the medial and the neointimal cell layers of rat carotid artery between day 7 and 14 after injury.…”

Section: Discussionmentioning

confidence: 99%

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Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries

Cheng

Kuzuya

Sasaki

et al. 2004

The American Journal of Pathology

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The matrix-degrading activity of several proteases are involved in the accelerated breakdown of extracellular matrix associated with vascular remodeling during the development of atherosclerosis and vascular injury-induced neointimal formation. Previous studies have shown that the potent elastolytic cysteine proteases, cathepsins S and K, are overexpressed in atherosclerotic lesions in human and animal models. However, the role of these cathepsins in vascular remodeling remains unclear. In the present study, the expressions of cathepsin S and K and their inhibitor cystatin C were examined during arterial remodeling using a rat carotid artery balloon-injury model. The increase in both cathepsin S and K mRNA levels was observed from day 1 and day 3 through day 14 following the induction of balloon injury, respectively. Western blotting analysis revealed that both cathepsin S and K protein levels also increased in the carotid arteries during neointima formation, coinciding with an increase elastolytic activity assayed using Elastin-Congo red, whereas, no significant change in the expressions of cystatin C mRNA and protein was observed during follow-up periods after injury. Immunohistochemistry, Western blot, and in situ hybridization showed that the increase of cathepins S and K and the decrease of cystatin C occurred preferentially in the developing neointima. These findings suggest that cathepsin S and K may participate in the pathological arterial remodeling associated with restenosis.

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mentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries

Cheng

Kuzuya

Sasaki

et al. 2004

The American Journal of Pathology

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“…However, the release of VEGF and of activated MMP2 by SMC, in response to IL-3 challenge, substantially contributed to the migratory effect exerted by the CM on EC. The collagenase IV degrading enzyme MMP2 is known to act by degrading the component of the basement membrane to which EC attach (Lewalle et al, 1995;Kenagy et al, 1997). Thus, IL-3 by inducing MMP2 activity, might render EC competent to the chemoattractant effect of VEGF leading to EC migration.…”

Section: Discussionmentioning

confidence: 99%

“…IL-3 and vessel stabilization P Dentelli et al IL-3 stimulates MMP2 enzymatic activity and VEGF synthesis both in EC and SMC MMP-2, which is secreted by EC and SMC (Lewalle et al, 1995;Kenagy et al, 1997), can participate, upon activation from the latent zymogen form, in the degradation of interstitial collagen thus regulating cell migration. To evaluate whether differences in MMP2 activity might account for the effects on EC and SMC migration, CM from IL-3-stimulated EC and SMC were assayed for gelatin-zymography.…”

Section: Motogenic Response To CM From Il-3-stimulated Cellsmentioning

confidence: 99%

IL-3 affects endothelial cell-mediated smooth muscle cell recruitment by increasing TGFβ activity: potential role in tumor vessel stabilization

et al. 2004

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Interleukin-3 (IL-3) expression by tumor-infiltrating lymphocytes (TILs) and its effects on vessel assembly were evaluated. TILs from 'in situ' human breast cancers expressed CD4/CD25 antigens and IL-3. An injection of Matrigel containing SMC and IL-3 or basic-fibroblast growth factor (bFGF) into SCID mice confirmed the neoangiogenetic effect of both factors. However, in response to IL-3, but not to bFGF, only few SMC became incorporated into the nascent vessels. To evaluate the possibility that signals emanated by the nascent vasculature in the presence of IL-3 may negatively regulate SMC recruitment, conditioned media (CM) from IL-3-treated endothelial cells (EC) or SMC were tested for their biological effects on SMC and EC. CM from IL-3-treated SMC stimulated the migration of EC. In contrast, the migration of SMC was not affected by CM from IL-3-stimulated EC; however, it was greatly enhanced by blocking transforming growth factor b (TGFb) activity. TGFb immunoenzymatic assay demonstrated the following: (i) the absence of TGFb activity in CM from IL-3-stimulated EC; (ii) a barely detectable TGFb activity in CM from IL-3-stimulated SMC; and (iii) the presence of TGFb activity in the supernatants of SMC stimulated with CM from IL-3-, but not from bFGF-stimulated EC. Increased TGFb mRNA expression was only detected in SMC stimulated with CM from IL-3-treated EC. Finally, the inhibitory signals induced by IL-3 in vivo were abrogated by the addition of the neutralizing TGFb antibody. Thus, the positive immunostaining for IL-3 by TILs in 'in situ' breast cancers sustains the possibility that early in tumor development, IL-3 can contribute to the chronic immaturity of these vessels.

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“…Therefore we speculated that activation of an autocrine/ paracrine growth factor-dependent loop might underlie the observed biological effects, as a consequence of FGF-2 induction. FGF-2 is known to stimulate secretion of matrix degrading proteins in both endothelial and smooth muscle cells 62,63 and this may explain the MMP-9 increase observed in wtE1A-transfected cells. In fact, anti-FGF-2 neutralizing antibodies reduced the amount of MMP-9 released in the CM of transfected BAEC ( Figure 4C) however they did not influence the migration/invasion capacity of transfected cells (not shown).…”

Section: Discussionmentioning

confidence: 99%

E1A stimulates FGF-2 release promoting differentiation of primary endothelial cells

et al. 2000

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Basic Fibroblast Growth Factor (FGF-2) is a growth and survival factor and represents one of the most potent differentiation agents of vascular system. In the present study we describe that adenoviral oncoprotein E1A regulates FGF-2 production and determines the acquisition of a proangiogenic phenotype in primary bovine aortic endothelial cells (BAEC). Following their transfection, wild type E1A proteins 12S and 13S (wtE1A) stimulated BAEC to differentiate on reconstituted basement membrane matrix (Matrigel). This outcome was paralleled by invasion and migration enhancement in wtE1A-transfected cells. This stimulating effect was absent with the E1A mutant dl646N. Accordingly, zymography and RT ± PCR analyses showed that matrix metalloproteinase-9 protein-and mRNA-levels increased following wtE1A transfection. Interestingly, wtE1A-transfected BAEC showed FGF-2 mRNA-and protein-levels higher than controls. Further, FGF-2 neutralization reduced the amount of MMP-9 released in the supernatant of E1A-transfected cells and strongly inhibited BAEC differentiation, thus suggesting that wtE1A activates BAEC by a mechanism, at least partially, dependent on a FGF-2 autocrine/paracrine loop. Cell Death and Differentiation (2000) 7, 292 ± 301.

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Primate Smooth Muscle Cell Migration From Aortic Explants Is Mediated by Endogenous Platelet-Derived Growth Factor and Basic Fibroblast Growth Factor Acting Through Matrix Metalloproteinases 2 and 9

Abstract: These data demonstrate that SMC migration from primate aortic explants is dependent on endogenous MMP2, MMP9, PDGF, and bFGF. The data also suggest that PDGF-induced (PDGF-BB or possibly PDGF-AB) migration is dependent on MMP2, whereas bFGF-induced migration depends on both MMP2 and MMP9.

Cited by 136 publications

References 62 publications

Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries

Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries

IL-3 affects endothelial cell-mediated smooth muscle cell recruitment by increasing TGFβ activity: potential role in tumor vessel stabilization

E1A stimulates FGF-2 release promoting differentiation of primary endothelial cells

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