Superficial pseudoaneurysms: clinicopathologic aspects and involvement of extracellular matrix proteoglycans

Burke, Allen; Järveläinen, Hannu; Kolodgie, Frank D.; Goel, Ashita; Wight, Thomas N.; Virmani, Renu

doi:10.1038/modpathol.3800060

Cited by 21 publications

(22 citation statements)

References 18 publications

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“…Several studies have supported a proangiogenic role for decorin and, in particular, in angiogenesis associated with inflammatory conditions. 18,[23][24][25][26] This is noteworthy as obesity has been associated with inflammation of the adipose tissue. 27 Decorin may, therefore, have a proangiogenic role during adipose tissue expansion in times of positive energy balance.…”

Section: Discussionmentioning

confidence: 99%

Decorin is a secreted protein associated with obesity and type 2 diabetes

et al. 2008

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Objective: To characterize the expression of the small leucine-rich glycoprotein decorin in adipose tissue. Design: Real-time PCR was used to measure decorin gene expression in adipose tissue from normal glucose tolerant (NGT), impaired glucose tolerant and type 2 diabetic (T2D) Psammomys obesus. Adipose tissue was fractionated to determine which cells were responsible for decorin expression. The location of decorin protein expression in adipose tissue was determined using immunohistochemistry. Real-time PCR was used to measure decorin mRNA levels in human adipose tissue from 16 insulinsensitive, 16 insulin-resistant and 6 T2D human subjects. Circulating plasma decorin concentrations were measured by enzymelinked immunosorbent assay in 145 NGT and 141 T2D human individuals from a large-scale epidemiological study in Mauritius. Results: Decorin mRNA was found to be highly expressed in adipose tissue, and decorin gene expression was significantly higher in visceral than that in subcutaneous adipose tissue depots in both P. obesus and human subjects (P ¼ 0.002 and P ¼ 0.001, respectively). Decorin mRNA was predominantly expressed by stromal/vascular cells of adipose tissue, and decorin protein in adipose tissue was primarily detected adjacent to blood vessels. Circulating plasma decorin levels in humans were elevated by 12% in T2D (P ¼ 0.049) compared to NGT subjects. There was a significant independent correlation between plasma decorin levels and waist-to-hip ratio (WHR, P ¼ 0.024). In male subjects, plasma decorin levels were significantly correlated with WHR (P ¼ 0.006), and fasting and 2-h glucose levels in an oral glucose tolerance test (P ¼ 0.027 and P ¼ 0.001, respectively). Conclusions: Decorin expression in adipose tissue was markedly upregulated in the obese state and may therefore play a role in adipose tissue homeostasis or in pathophysiology associated with obesity.

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Section: Discussionmentioning

confidence: 99%

Decorin is a secreted protein associated with obesity and type 2 diabetes

et al. 2008

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“…Furthermore, decorin positive microvessels have been detected at the base of pseudoaneurysms in the temporal artery of human patients [84]. Decorin has also been found to be expressed in significant amounts around neovessels after varicose vein surgery in patients [85].…”

Section: Decorin In Angiogenesismentioning

confidence: 99%

Pivotal role for decorin in angiogenesis

2015

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Angiogenesis, the formation of new blood vessels from preexisting vessels, is a highly complex process. It is regulated in a finely-tuned manner by numerous molecules including not only soluble growth factors such as vascular endothelial growth factor and several other growth factors, but also a diverse set of insoluble molecules, particularly collagenous and non-collagenous matrix constituents. In this review we have focused on the role and potential mechanisms of a multifunctional small leucine-rich proteoglycan decorin in angiogenesis. Depending on the cellular and molecular microenvironment where angiogenesis occurs, decorin can exhibit either a proangiogenic or an antiangiogenic activity. Nevertheless, in tumorigenesis-associated angiogenesis and in various inflammatory processes, particularly foreign body reactions and scarring, decorin exhibits an antiangiogenic activity, thus providing a potential basis for the development of decorin-based therapies in these pathological situations.

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“…84,85 Thus, late phase aneurysmal development may involve selective loss of versican. Pseudoaneurysms of the temporal artery show increased immunostaining for versican in areas where there is elastic fiber interruption, 86 indicating a possible early involvement of versican in remodeling involving elastogenesis ( Figures 2E and 2F). Interestingly, ASMCs cultured from aneurysmal aortas synthesize elevated levels of versican.…”

Section: Aneurysmsmentioning

confidence: 99%

Proteoglycans in Atherosclerosis and Restenosis

Wight

Merrilees

2004

Circulation Research

334

243

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Abstract-The proteoglycan versican is one of several extracellular matrix (ECM) molecules that accumulate in lesions of atherosclerosis and restenosis. Its unique structural features create a highly interactive molecule that binds growth factors, enzymes, lipoproteins, and a variety of other ECM components to influence fundamental events involved in vascular disease. Versican is one of the principal genes that is upregulated after vascular injury and is a prominent component in stented and nonstented restenotic lesions. The synthesis of versican is highly regulated by specific growth factors and cytokines and the principal source of versican is the smooth muscle cell. Versican interacts with hyaluronan, a long chain glycosaminoglycan, to create expanded viscoelastic pericellular matrices that are required for arterial smooth muscle cell (ASMC) proliferation and migration. Versican is also prominent in advanced lesions of atherosclerosis, at the borders of lipid-filled necrotic cores as well as at the plaque-thrombus interface, suggesting roles in lipid accumulation, inflammation, and thrombosis. Versican influences the assembly of ECM and controls elastic fiber fibrillogenesis, which is of fundamental importance in ECM remodeling during vascular disease. Collectively, these studies highlight the critical importance of this specific ECM component in atherosclerosis and restenosis. Key Words: proteoglycans Ⅲ versican Ⅲ extracellular matrix Ⅲ atherosclerosis Ⅲ smooth muscle cells V ersican is a chondroitin sulfate proteoglycan (CSPG) that is present in the extracellular matrix (ECM) of normal blood vessels and increases dramatically in all forms of vascular disease. 1,2 A number of reports within the last few years have documented a significant involvement of versican in lesions of atherosclerosis and restenosis and these observations, coupled to those that demonstrate that this ECM proteoglycan regulates many of the events that contribute to the formation of atherosclerotic and restenotic lesions, highlights the critical importance of versican in the pathogenesis of vascular disease.Versican is one of many proteoglycans identified in vascular tissue or synthesized by vascular cells 3 and together with biglycan, decorin, and perlecan constitute the bulk of the proteoglycans found in the interstitial space. 2 Versican interacts with hyaluronan, a long chain high molecular weight glycosaminoglycan (GAG), that is also present in the extracellular matrix (ECM) of blood vessels and increases as versican in vascular disease. 4 The versican gene and protein follow a domain template. The amino-terminal globular domain (G1) binds hyaluronan, and the carboxy-terminal globular domain (G3) resembles the selectin family of proteins, consisting of a C-type lectin adjacent to two epidermal growth factor (EGF) domains and a complement regulatory region. The middle region of the versican core protein is encoded by two large exons that specify the chondroitin sulfate attachment regions of versican (Figure 1). These highly interactiv...

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Superficial pseudoaneurysms: clinicopathologic aspects and involvement of extracellular matrix proteoglycans

Cited by 21 publications

References 18 publications

Decorin is a secreted protein associated with obesity and type 2 diabetes

Decorin is a secreted protein associated with obesity and type 2 diabetes

Pivotal role for decorin in angiogenesis

Proteoglycans in Atherosclerosis and Restenosis

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