Expression of Extracellular Matrix Proteins Accompanies Lesion Growth in a Model of Intimal Reinjury
TL;DR: It is demonstrated that the accumulation of extracellular matrix is important in the increase in lesion size after reinjury and that a balance of matrix synthesis and degradation may explain why no change in matrix volume was detected until 28 days after the reinjury.
Abstract: —Reinjury of rat arterial lesions induces an increase in lesion size that is not associated with an increase in cell number. In this study, matrix volume was examined after reinjury to preexisting lesions, and the kinetics of matrix gene expression and activity of proteolytic enzymes in the lesion were evaluated. Volume densitometry in intima showed a significant increase in matrix volume 28 days after the reinjury, although no change was observed at 14 days. Three common vascular matrix molecules, α1(I)procollagen, tropoelastin, and fibronectin, were expressed highly at 7 days after the reinjury. Expression of tropoelastin remained upregulated for the entire 28 days after the reinjury, whereas α1(I)procollagen and fibronectin returned to the control level by 28 days. Protease activity was also increased after reinjury. Within days, a marked increase in urokinase plasminogen activator activity was observed in intima, and this activity decreased to control level by 14 days. The activity of tissue p...
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TL;DR: An increase in cell replication is critical in the development of in-stent restenosis, and that inflammatory responses represent a unique property after stent implantation are suggested.
8 citations
Cites methods from "Expression of Extracellular Matrix ..."
...The lysates of carotid arteries were also subjected to plasminogen activator (PA) zymography and gelatin zymography, as described previously [6]....
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01 Jan 2005
TL;DR: The vein wall matrix metalloproteinase gene and activity response induced over time in the vein wall after DVT is described and the corresponding collagen upregulation and proximate plasmin system mediators are determined.
Abstract: Hypothesis: Deep venous thrombosis (DVT) confers vein wall injury associated with fibrosis and extracellular matrix (ECM) turnover, likely mediated by matrix proteases. This study investigated the expression of proteases and collagen involved in early vein wall remodeling. Methods: In the mouse, DVT was produced by ligation of the infrarenal inferior vena cava (IVC) or sham operation, and tissue was harvested at 4, 8, and 12 days. The vein wall tissue was processed for real-time reverse transcriptase-polymerase chain reaction (6 to 8 per time point), Western immunoblotting (5 per time point), and gelatin zymography (5 per time point). Analysis of variance was used for multiple comparisons, and a P <.05 was significant. Results: Thrombus resolution was documented by a 38% decrease in the thrombosed IVC weight from day 4 to day 12 (P =.007). Total vein wall collagen increased over time, with a corresponding increase in procollagen I and III, and expression peaked at 12 days (24-fold and 6.1-fold, respectively, P <.02). Matrix metalloproteinase-2 (MMP-2) gene expression was 23-fold greater at 12 days after thrombus formation compared with sham or 4 days after thrombosis (P <.05). Total MMP-2 activity was also significantly elevated at 12 days compared with sham (P <.05). MMP-9 expression was 19-fold and 27-fold higher at days 4 and 8, respectively, relative to sham (P <.05), with no difference in activity. MMP-14 expression was twofold to 3.6-fold greater at day 12 compared with earlier time points and shams (P <.001), but no differences in protein levels were found. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) protein levels were not significantly different from sham over time; however, the ratio of uPA to PAI-1 was decreased through 8 days. Conclusions: Vein wall remodeling after DVT is similar to wound healing and is associated with increased procollagen gene expression and total collagen. It is also associated with increased early MMP-9 expression, followed by MMP-2 expression and activity after DVT resolution. (J Vasc Surg 2005;42:140-8.) Clinical Relevance: Deep vein thrombosis is an often neglected problem that long term is associated with the postphlebitic syndrome of limb swelling, pain, and often ulceration. The basic mechanisms of the vein wall damage that results have not been delineated. The following study describes the vein wall matrix metalloproteinase gene and activity response induced over time in the vein wall after DVT. Additionally, the corresponding collagen upregulation and proximate plasmin system mediators are determined. With this knowledge, potential therapies to reduce vein wall injury directly might be possible.
7 citations
TL;DR: Data indicate that vascular hyporeactivity induced by mechanical injury may be due to alterations of either [Ca(2+)](i) or contractile proteins.
4 citations
TL;DR: Evidence supporting the role of PTX3 in predicting primary cardiovascular events and diagnosis and prognosis of cancer is discussed.
Abstract: Inflammatory mediators may play key roles in both atherosclerosis and cardiovascular disorders and in cancer development. Pentraxins are a family of proteins characterized by the structural motif pentraxin domain. Long pentraxin 3 (PTX3), a protein that in humans is encoded by the PTX3 gene, is rapidly produced and released by several cell types in response to inflammatory stimuli. This review discusses the evidence supporting the role of PTX3 in predicting primary cardiovascular events and diagnosis and prognosis of cancer.
3 citations
Cites background from "Expression of Extracellular Matrix ..."
...The FGF/FGFR system plays a crucial role not only in FGF2-dependent ECs proliferation [22] but also in SMCs proliferation, migration and survival in vitro [23-26]....
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References
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Journal Article•
TL;DR: The concept that intimal SMC proliferation after arterial injury is an acute event related to the initial injury process is supported, as persistent proliferation of luminal SMC does not result in an increase in intimal cell number.
1,509 citations
TL;DR: It is demonstrated that endogenous PDGF is involved in the accumulation of neointimal smooth muscle cells associated with balloon injury and may be involved in restenosis after angioplasty, and perhaps in atherogenesis as well.
Abstract: Approximately 30 to 40 percent of atherosclerotic coronary arteries treated by angioplasty or by bypass surgery occlude as a result of restenosis. This restenosis is due principally to the accumulation of neointimal smooth muscle cells, which is also a prominent feature of the advanced lesions of atherosclerosis. The factors responsible for the accumulation of intimal smooth muscle cells have not been identified. Platelet-derived growth factor (PDGF) is a potent smooth muscle chemoattractant and mitogen. It is present in platelets and can be formed by endothelium, smooth muscle, and monocyte-derived macrophages. The development of an intimal lesion in the carotid artery of athymic nude rats induced by intraarterial balloon catheter deendothelialization was inhibited by a polyclonal antibody to PDGF. These data demonstrate that endogenous PDGF is involved in the accumulation of neointimal smooth muscle cells associated with balloon injury and may be involved in restenosis after angioplasty, and perhaps in atherogenesis as well.
1,088 citations
TL;DR: Restenosis is most prevalent between 1 and 3 months and rarely occurs beyond 3 months after coronary angioplasty and reached a plateau thereafter.
892 citations
TL;DR: Chemical cross-linking of CHO-conditioned medium and immunoblot analyses indicates that latent recombinant TGF beta 1 contains both the cleaved amino-terminal glycopeptide and mature TGFbeta 1 polypeptide in a noncovalent association and that this association confers latency.
Abstract: Medium conditioned by Chinese hamster ovary (CHO) cells transfected with the simian pre-pro-TGF beta 1 cDNA contains high levels of latent TGF beta 1. The amino-terminal region of the TGF beta 1 precursor is secreted and can be detected in the conditioned medium by immunoblotting using peptide antibodies specific for amino-terminal peptides. Chemical cross-linking of CHO-conditioned medium using bis-(sulfosuccinimidyl)-suberate (BS3) followed by immunoblot analyses indicates that latent recombinant TGF beta 1 contains both the cleaved amino-terminal glycopeptide and mature TGF beta 1 polypeptide in a noncovalent association and that this association confers latency. The data presented here do not support the involvement of a unique TGF beta binding protein(s) in latent recombinant TGF beta 1. Plasmin treatment of CHO-conditioned medium resulted in the appearance of TGF beta competing activity. In addition, immunoblot analysis of plasmin-treated CHO-conditioned medium indicates that the amino-terminal glycopeptide is partially degraded and that mature TGF beta 1 is released. Thus, activation of latent TGF beta 1 may occur by proteolytic nicking within the amino-terminal glycopeptide thereby causing a disruption of tertiary structure and noncovalent bonds, which results in the release of active, mature TGF beta 1. Acid activation of latent TGF beta, in comparison, appears to be due to dissociation of the amino-terminal glycopeptide from the mature polypeptide.
729 citations
TL;DR: There are at least three different fibronectin mRNAs in rat liver which differ in coding potential and are probably all encoded by a single gene, according to the sequence data and S1 nuclease mapping.
659 citations