Arterial Enlargement in Response to High Flow Requires Early Expression of Matrix Metalloproteinases to Degrade Extracellular Matrix

Sho, Eiketsu; Sho, Mien; Singh, Tej M.; Nanjo, Hiroshi; Komatsu, Masaki; Xu, Chengpei; Masuda, Hirotake; Zarins, Christopher K.

doi:10.1006/exmp.2002.2457

Cited by 170 publications

(163 citation statements)

References 36 publications

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“…Senior (37) assumed that structural cells of the lung were possible producers of enzymes that degrade lung tissue in emphysema. Recent reports demonstrate that MMP-2 plays a much longer and more important role in the degradation and fragmentation of internal elastic lamina (IEL) than MMP-9, even though both MMP-2 and MMP-9 had contributed to the degradation of the cell basement membrane in chronic flow-induced arterial enlargement (31). We hypothesize here that the production of MMP2 and MMP9 by lung fibroblasts may be involved the parthenogenesis of COPD, which is regulated by EGR1.…”

Section: Discussionmentioning

confidence: 75%

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Ning

Kaminski

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

301

269

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To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers. A total of 59,343 tags corresponding to 26,502 transcripts were sequenced in SAGE analyses. A total of 327 genes were differentially expressed (1.5-fold up-or down-regulated). Microarray analysis using the same RNA source detected 261 transcripts that were differentially expressed to a significant degree between GOLD-2 and GOLD-0 smokers. We confirmed the altered expression of a select number of genes by using real-time quantitative RT-PCR. These genes encode for transcription factors (EGR1 and FOS), growth factors or related proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix protein (COL1A1). Immunofluorescence studies on the same lung specimens localized the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding activity in human lung fibroblast cells. Cytomix (tumor necrosis factor ␣, IL-1␤, and IFN-␥) treatment showed that the activity of matrix metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGR1 control (؉/؉) mice but not detected in that of EGR1 null (؊/؊) mice, whereas MMP-9 was regulated by EGR1 in a reverse manner. Our study represents the first comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and reveals previously unreported candidate genes that may serve as potential molecular targets in COPD.

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Section: Discussionmentioning

confidence: 75%

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Ning

Kaminski

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

301

269

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“…Endothelial dysfunction initially and vascular remodeling subsequently are triggered by shear stress (Sho et al, 2002). This explains why IA is commonly found at arterial junctions, bifurcations or abrupt vascular angles where excessive hemodynamic stresses are exerted on arterial walls (Kondo et al, 1997).…”

Section: The Common Pathwaymentioning

confidence: 99%

Biology of Intracranial Aneurysms: Role of Inflammation

Chalouhi

Ali

Jabbour

et al. 2012

J Cereb Blood Flow Metab

443

418

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Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.

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“…1 The seeming relationship between elevated stresses and the preferential locations of cerebral aneurysm was further strengthened by research on the biologic response of the vessel wall to these mechanical stimuli. It has been suggested that normal functioning of the endothelial cells is mediated through WSS 5,14 and that high WSS is linked to different biologic reactions, such as increased metalloproteinase 15 and nitric oxide production, 16,17 which may play a role in pathologic vessel wall remodeling and aneurysm formation.…”

Section: Wssmentioning

confidence: 99%

Hemodynamics of Cerebral Aneurysm Initiation: The Role of Wall Shear Stress and Spatial Wall Shear Stress Gradient

Kulcsár

Ugron²,

Marosfői

et al. 2011

AJNR Am J Neuroradiol

197

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BACKGROUND AND PURPOSE:Cerebral aneurysms are preferentially located at arterial curvatures and bifurcations that are exposed to major hemodynamic forces, increasingly implicated in the life cycle of aneurysms. By observing the natural history of aneurysm formation from its preaneurysm state, we aimed to examine the hemodynamic microenvironment related to aneurysm initiation at certain arterial segments later developing an aneurysm.

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Arterial Enlargement in Response to High Flow Requires Early Expression of Matrix Metalloproteinases to Degrade Extracellular Matrix

Cited by 170 publications

References 36 publications

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Biology of Intracranial Aneurysms: Role of Inflammation

Hemodynamics of Cerebral Aneurysm Initiation: The Role of Wall Shear Stress and Spatial Wall Shear Stress Gradient

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