Expression of Lumican in Thickened Intima and Smooth Muscle Cells in Human Coronary Atherosclerosis

Onda, Munehiko; Ishiwata, Toshiyuki; Kawahara, Kiyoko; Wang, Ruojiao; Naito, Zenya; Sugisaki, Yuichi

doi:10.1006/exmp.2002.2425

Cited by 55 publications

(34 citation statements)

References 25 publications

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“…The arrowhead indicates the level of the intima/media boundary. Immunoreactivity corresponding to the class II SRL proteoglycan lumican has been observed in both atherosclerotic lesions and intimal hyperplasia (24). Consistent with these findings, by mass spectrometry lumican was detected in intimal hyperplasia in most of the specimens analyzed here.…”

Section: Fig 2 Removal Of Thickened Intima For Proteomic Analysissupporting

confidence: 90%

Analysis of Intimal Proteoglycans in Atherosclerosis-prone and Atherosclerosis-resistant Human Arteries by Mass Spectrometry

Talusan

Bedri

Yang

et al. 2005

Molecular & Cellular Proteomics

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The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. To determine a possible cause for such differences in atherosclerosis susceptibility, a proteomics-based approach was used to assess the extracellular proteoglycan core protein composition of intimal hyperplasia from both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan composition in these preatherosclerotic lesions was found to be more complex than previously appreciated with up to eight distinct core proteins present, including the large extracellular proteoglycans versican and aggrecan, the basement membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans biglycan and decorin, and the class II small leucine-rich proteoglycans lumican, fibromodulin, and prolargin/ PRELP (proline arginine-rich end leucine-rich repeat protein). Although most of these proteoglycans seem to be present in similar amounts at the two locations, there was a selective enhanced deposition of lumican in the intima of the atherosclerosis-prone internal carotid artery compared with the intima of the atherosclerosis-resistant internal thoracic artery. The enhanced deposition of lumican in the intima of an atherosclerosis prone artery has important implications for the pathogenesis of atherosclerosis.

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Section: Fig 2 Removal Of Thickened Intima For Proteomic Analysissupporting

confidence: 90%

Analysis of Intimal Proteoglycans in Atherosclerosis-prone and Atherosclerosis-resistant Human Arteries by Mass Spectrometry

Talusan

Bedri

Yang

et al. 2005

Molecular & Cellular Proteomics

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“…Our previous results suggesting that fibromodulin is involved in plaque development by affecting ECM structure and lipid retention, together with previous publications discussing lumican expression in healthy and pathological vasculature, [17][18][19][20][21] raise the question of possible contribution by these SLRPs to atherosclerotic plaque development and its stability. In the present study we have thus for the first time analyzed the expression of fibromodulin and lumican in human carotid plaques in relation to the occurrence of preoperative cerebrovascular symptoms (namely strokes, transient ischemic attacks (TIA) or amaurosis fugax) and postoperative cardiovascular (CV) events.…”

Section: Introductionmentioning

confidence: 66%

“…17 In addition, lumican has been shown to be expressed in intimal vascular SMCs in human coronary atherosclerosis 18 and, as compared to arteries from healthy subjects, overexpressed in arteries from patients with coronary artery dis-ease, 19 in femoral arteries with atherosclerotic plaques from patients with peripheral occlusive arterial disease 20 and in aortic valves from patients with degenerative aortic stenosis 21 .…”

Section: Discussionmentioning

confidence: 99%

Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events

et al. 2015

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Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events.Shami, Annelie; Tengryd, Christoffer; Asciutto, Giuseppe; Bengtsson, Eva; Nilsson, Jan; Hultgårdh, Anna; Goncalves, Isabel Link to publication Citation for published version (APA): Shami, A., Tengryd, C., Asciutto, G., Bengtsson, E., Nilsson, J., Hultgårdh, A., & Goncalves, I. (2015). Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events. Atherosclerosis, 241(2), 701-708. DOI: 10.1016701-708. DOI: 10. /j.atherosclerosis.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ABSTRACTAims The small leucine-rich proteoglycans fibromodulin and lumican are functionally related extracellular matrix proteins involved in the regulation of collagen fiber formation. Fibromodulin-deficient apolipoprotein E-null mice have decreased vascular retention of lipids and reduced development of atherosclerosis suggesting that fibromodulin may influence the disease process. The aim of the present study was to investigate if fibromodulin and lumican are expressed in human carotid plaques and to determine if their expression is associated with the occurrence of preoperative symptoms and with risk for postoperative cardiovascular events.Methods and Results 153 plaques (51% symptomatic) obtained by carotid endarterectomy were included in this study. Plaque content was analyzed by immunohistochemistry and plaque cytokine content by multiplex technology. Fibromodulin and lumican were widely expressed in plaques and fibromodulin expression was significantly higher in symptomatic plaques. Expression of fibromodulin was significantly higher in plaques obtained from patients with diabetes and a high fibromodulin expression was associated with a higher incidence of post-operative cerebrovascular events, whereas no such associations were seen for lumican. Fibromodulin expression also correlated with plaque lipids and several pro-inflammatory cytokines. In addition, fibromodulin expression correlated with low levels of smooth muscle cells and the antiinflammatory cytokine IL-10.Conclusions These observations support previous experimental findings in mice for a role of fibromodulin in atherosclerosis and provide clinical evidence of the involvement of fibromodulin in the inflammatory processes that characterize atherosclerotic plaque vulnerability. They also suggest that this is of particular importance in diabetes.

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“…cornea (Kao and Liu, 2002) Cornea plana (Pellegata et al, 2000) Osteoarthritis Lumican Structural component of e.g. cornea (Kao and Liu, 2002) Myopia Majava et al, 2007a) Fibrosis and tumor growth (Naito, 2005); atherosclerosis (Onda et al, 2002) Osteoadherin Promotes ␣v/␤3-integrin mediated cell binding (Wendel et al, 1998); regulation of complement activation (Sjöberg et al, 2009) PRELP Anchors basement membranes to the underlying connective tissue (Bengtsson et al, 2002) Myopia (Majava et al, 2007a) Epiphycan Involved in chondrogenesis (Knudson and Knudson, 2001) Opticin Component of the vitreous humour of the eye (Reardon et al, 2000) and cartilage (Monfort et al, 2008) Myopia (Majava et al, 2007a); primary open angle glaucoma (Acharya et al, 2007) Osteoglycin/Mimecan Component of the vascular wall (Shanahan et al, 1997); regulation of collagen fibrillogenesis (Tasheva et al, 2002) Chondroadherin Component of the cornea, brain, and skeletal muscle, retina and lens (Tasheva et al, 2004); regulates chondrocyte growth and proliferation (Shen et al, 1998) Nyctalopin Essential for retinal synaptic transmission …”

Section: Targeting Extracellular Matrix Molecules In Pharmacotherapymentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Järveläinen

Sainio

Koulu

et al. 2009

Pharmacological Reviews

457

338

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Expression of Lumican in Thickened Intima and Smooth Muscle Cells in Human Coronary Atherosclerosis

Cited by 55 publications

References 25 publications

Analysis of Intimal Proteoglycans in Atherosclerosis-prone and Atherosclerosis-resistant Human Arteries by Mass Spectrometry

Analysis of Intimal Proteoglycans in Atherosclerosis-prone and Atherosclerosis-resistant Human Arteries by Mass Spectrometry

Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

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