Role of Extracellular Vesicles in De Novo Mineralization

Abstract

Extracellular vesicles are membrane micro/nanovesicles secreted by many cell types into the circulation and the extracellular milieu in physiological and pathological conditions. Evidence suggests that extracellular vesicles, known as matrix vesicles, play a role in the mineralization of skeletal tissue, but emerging ultrastructural and in vitro studies have demonstrated their contribution to cardiovascular calcification as well. Cells involved in the progression of cardiovascular calcification release active vesicles capable of nucleating hydroxyapatite on their membranes. This review discusses the role of extracellular vesicles in cardiovascular calcification, and elaborates on this additional mechanism of calcification as an alternative pathway to the currently accepted mechanism of biomineralization via osteogenic differentiation.

In Situ Vascular Tissue Remodeling Using Biodegradable Tubular Scaffolds With Incorporated Growth Factors and Chemoattractant Molecules

“…Similar patterns have been described both in clinical studies [14] and in in vitro studies [24]. However, some researchers state that dynamic stress promotes the development of calcification, but it is not its primary cause [13].…”

“…Recent studies have shown that cardiovascular calcification is triggered through the activation of cellular processes in the presence of an uncontrolled pathological environment that cannot be reproduced in the in vitro models. Therefore, it limits the opportunities to investigate the cause-effect relationships, mostly studied by the endpoints of the affected tissues [14,15]. Smooth muscle cells are considered to be the main source of origin of osteogenic cells in calcified vascular lesions [16].…”

“…In vitro and ex vivo studies have established the involvement of inflammation in the calcification of both valves and vessels [19,20]. Calcification in these tissues follows the accumulation of macrophages, and its final stage is accompanied by the induction during inflammation [14]. Importantly, a new concept suggesting that progenitor cells circulating in the blood under certain conditions can exhibit their osteogenic potential and promote intimal [21] and valvular calcification [22] has recently emerged.…”

“…It was shown that with increasing progression of aortic valve stenosis, the number of circulating osteocalcin-positive endothelial progenitor cells (CD34 + / OCN +) increased with their subsequent accumulation in the calcified aortic valve tissue [22]. Thus, this cascade results in the deposition of calcium, primarily in the zones with critical stress [14].…”

A current understanding of vascular calcification in CKD

“…They contain the same enzymes such as tissue nonspecific alkaline phosphatase which are critical in altering the local microenvironment to precipitate ectopic calcification (75). These pathological MV are also dependent on annexins II, V, and VI for mineral deposition identical to MV from normal osteoblasts and chondrocytes (12).…”