Decorin Is Produced by Capillary Endothelial Cells in Inflammation-Associated Angiogenesis

Abstract

Decorin is a small extracellular chondroitin/dermatan sulfate proteoglycan that has previously been shown to be involved in the angiogenesis-like behavior of endothelial cells (ECs) in vitro. There is also evidence that decorin plays a role in angiogenesis in vivo. In this study we sought to further explore the involvement of decorin in angiogenesis in vivo, especially in that associated with inflammation. We found by CD31 immunostaining of ECs that in giant cell arteritis there are capillary blood vessels not only in the adventitia as in uninvolved temporal artery wall, but also in the media and the external zone of the thickened intima. Localization of decorin by antiserum LF-30 in adjacent sections showed that in normal temporal artery wall decorin resides mainly in the media and the adventitia, whereas in inflamed temporal artery wall decorin is distributed throughout the vessel wall including the intima. Furthermore, the most intense reaction for decorin was evident in ECs of capillary neovessels within the media and the thickened intima of inflamed temporal artery wall. Decorin was also found in capillary ECs in certain pathological and physiological conditions in which the pivotal role of angiogenesis is more generally accepted. Pyogenic granulomas, granulation tissue of healing dermal wounds, and ovaries at different phases of follicle and corpus luteum formation all contained widely distributed CD31-positive capillaries. Decorin, on the other hand, was found in capillary ECs in pyogenic granulomas and granulation tissue, but not in those in the ovaries. The assessment of the degree of inflammation in the specimens with the presence of CD68-positive macrophages showed that the pyogenic granuloma, granulation tissue, and giant cell arteritis specimens were rich in macrophages around the decorin-positive capillaries. In contrast, the ovarian specimens were populated with fewer macrophages and even they were not located in close vicinity of capillaries negative for decorin. Our results confirm that decorin is involved in angiogenesis in vivo and, particularly, in conditions in which the inflammatory component is dominant.

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

“…16 The stromal/ vascular cells found in adipose tissue comprise a range of cell types, including endothelial and smooth muscle cells associated with blood vessels, preadipocytes and inflammatory cells such as macrophages. As some of these cell types, such as endothelial cells, are known to express decorin in other tissues, 17,18 it is tempting to speculate that these cells are a major source of decorin expression in adipose tissue. Further studies using flow cytometry or immunohistochemistry with cell population-specific markers will be required to conclusively determine the source of decorin expression in adipose tissue.…”

“…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.…”

“…[33][34][35][36] It is therefore noteworthy that decorin has been shown to act as a proinflammatory factor and is produced at sites of inflammation. 18,[37][38][39][40][41] In contrast, Decorin, obesity and type 2 diabetes K Bolton et al decorin has also been reported to bind and inhibit the proinflammatory activity of the complement protein C1q 42 and has been hypothesized to antagonize C1q-induced insulin resistance in adipose tissue that is associated with obesity. 16 These observations indicate that decorin may play a role in inflammation associated with obesity in adipose tissue; however, this is likely to be a complex interaction between pro-and anti-inflammatory activities.…”

Decorin suppresses tumor cell-mediated angiogenesis

“…When cultured, however, macro-vascular endothelial cells spontaneously change their morphology from a polygonal to a sprouting phenotype and concurrently initiate decorin biosynthesis, thus suggesting that decorin might play a role in angiogenesis (Ja¨rvela¨inen et al, 1992). Moreover, decorin is produced by capillary endothelial cells during angiogenesis associated with profound inflammatory processes (Nelimarkka et al, 2001). Recent reports, however, point to a dual role of decorin as either proor anti-angiogenic factor.…”

Superficial pseudoaneurysms: clinicopathologic aspects and involvement of extracellular matrix proteoglycans

“…22 Recent studies show that decorin is required for angiogenesis in vitro. 23 Furthermore, decorin synthesis is upregulated when endothelial cells sprout and form tubes in vitro.…”