The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study

Abstract

Calcification and fibrointimal proliferation are associated with advanced complicated atherosclerosis in large arteries but may also occur in smaller vessels, resulting in ischaemic tissue necrosis. This study investigates whether the mechanisms of calcification and intimal fibrosis are similar in vessels of different sizes. The localization of osteopontin (OPN), matrix Gla protein (MGP), thrombospondin‐1 (TSP‐1), and cartilage oligomeric matrix protein (COMP) was investigated in three types of human vascular lesions: atherosclerosis, chronic vascular rejection (CVR) in renal allografts, and calcific uraemic arteriolopathy (calciphylaxis). These lesions were chosen as they affect different sized blood vessels and they exhibit a fibroproliferative intimal reaction, with or without calcification, resulting in luminal obliteration and ischaemic complications. OPN, MGP, TSP‐1, and COMP were not detected in normal blood vessels. However, OPN and MGP were expressed at sites of calcification within atherosclerotic lesions and in microvessels in calciphylaxis, suggesting that calcification in different sized vessels may occur by a common mechanism. These proteins were not detected in areas of fibrointimal proliferation. In contrast, TSP‐1 was localized primarily within the fibrous tissue of atherosclerotic lesions and was also expressed in the expanded fibrous intima of arteries showing CVR. COMP was localized primarily within the fibrous tissue under the lipid core of the majority of advanced atherosclerotic lesions. TSP‐1 and COMP were also detected in areas of microcalcification in atherosclerotic lesions and TSP‐1 was detected adjacent to areas of calcification in calciphylaxis. However, neither TSP‐1 nor COMP was localized to calcific foci within these lesions. The localization of OPN, MGP, TSP‐1, and COMP to pathological, but not normal arterial intima supports a pathogenetic role for these proteins in the development of vascular fibrosis and calcification. Modulation of their production and activity may offer a novel approach to the therapy of a number of vascular diseases. Copyright © 2001 John Wiley & Sons, Ltd.

Calcification in atherosclerosis: Bone biology and chronic inflammation at the arterial crossroads

“…However, fibrous-cap atheromatous lesions and fibrocalcific plaques express high levels of many of these proteins, particularly in regions of plaque where calcification is seen. Lamellar bone-like structures containing osteoblast-like cells may be found in association with matrix vesicles, and high expression of bone-matrix proteins in regions adjacent to mineralized plaque has been reported (19,30). Collectively, these findings support the concept that arterial calcification occurs in plaque microenvironments in a manner that recapitulates osteogenesis.…”

Chondrogenic and Adipogenic Potential of Microvascular Pericytes

“…Finally, pericytes may be involved in the development and progression of several pathological conditions, including vascular calcification. 30,31 Indeed, markers of both cartilage and bone have been identified in calcified blood vessels, [31][32][33][34][35] and it has been suggested that a subpopulation of SM cells that resemble pericytes (calcifying vascular cells) contributes to this calcification. 30 -32 A recent study has shown that these cells also have multilineage potential in vitro.…”

Vascular Calcification

“…It is interesting that evidence for similar expression patterns in calcified human arteries have recently been reported. Osteopontin levels were increased (25,26) and ␣ smooth muscle actin levels were decreased (25) in calcified medial layers of cutaneous blood vessels in patients with calcific uremic arteriolopathy. Furthermore, staining for osteopontin and other bone matrix molecules was strongly correlated with medial calcification in epigastric arteries of dialysis patients (27).…”