Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin?

Abstract

Over recent years, the role of matrix vesicles in the initial stages of arterial calcification has been recognized. Matrix calcifying vesicles have been isolated from atherosclerotic arteries and the biochemical composition of calcified vesicles has been studied. No studies have yet been carried out to examine the fine structure of matrix vesicles in order to visualize the features of the consequent stages of their calcification in arteries. In the present work, a high resolution ultrastructural analysis has been employed and the study revealed that matrix vesicles in human atherosclerotic lesions are heterogeneous with two main types which we classified. Type I calcified vesicles were presented by vesicles surrounded by two electron-dense layers and these vesicles were found to be resistant to the calcification process in atherosclerotic lesions in situ. Type II matrix vesicles were presented by vesicles surrounded by several electron-dense layers and these vesicles were found to represent calcifying vesicles in atherosclerotic lesions. To test the hypothesis that calcification of matrix vesicles surrounded by multilayer sheets may occur simply as a physicochemical process, independently from the cell regulation, we produced multilamellar liposomes and induced their calcification in vitro in a manner similar to that occurring in matrix vesicles in atherosclerotic lesions in situ.

Calcifying nanoparticles promote mineralization in vascular smooth muscle cells: implications for atherosclerosis

“…Both are localized to vascular plaque in vivo and increase in response to pathological elevations in extracellular mineral. 16,24,25,52,53 Smooth-muscle-derived matrix vesicles may also serve as nucleation foci for Ca deposition. 6,53 However, it is yet unknown whether CNPs act in combination with matrix vesicles to promote calcification.…”

“…Additionally, membrane-bound microvesicles, primarily shed from platelets, are present in the circulation, and microvesicles of leukocyte, endothelial, and smooth muscle origin accumulate within atherosclerotic plaques. 9,52 Evidence that these microvesicles participate directly in vascular calcification are lacking; however, circulating endothelial microvesicles impair endothelial function, 54,55 and plaque microvesicles, which are more concentrated than those in the circulation, are more thrombogenic, 9 thus contributing to atherosclerosis through proinflammatory and procoagulant mechanisms.…”

Role of Extracellular Vesicles in De Novo Mineralization

“…Concentrations of extracellular calcium and phosphate, similar to those found in serum of CRD patients on dialysis, induce the release of calcifying MVs from cells involved in cardiovascular calcification, such as vascular SMCs and macrophages (14, 15). The plaques of non-CRD patients also may contain MVs (39), suggesting that this phenomenon also occurs in an atherosclerotic or diabetic milieu.…”

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries

“…The shedding of membrane-surrounded microfragments of the cytoplasm from intact SMCs (Bobryshev et al 1995) together with apoptosis and the necrosis of arterial cells have been shown to be accompanied by the accumulation of a large number of matrix vesicles in the extracellular matrix of atherosclerotic lesions (Proudfoot et al 2001;Bobryshev 2005b). Matrix vesicles have been recognized as a structural basis for the initial stages of the formation of microcalcifications (Bobryshev et al 1995(Bobryshev et al , 2007Hsu and Camacho 1999;Proudfoot et al 2001;Anderson 2003).…”