K23 - Characterizing Molecular Differences in Vascular and Bone Calcification Pathways

Introduction: : Vascular calcification (VC)—the deposition of hydroxyapatite mineral in the arterial wall—is a clinically significant risk factor for cardiovascular events, yet no approved therapies exist for its prevention or treatment. Pathogenic vascular smooth muscle cells (VSMCs) drive this calcification process by releasing small, calcific extracellular vesicles into the surrounding extracellular matrix, mirroring homeostatic mechanisms observed in bone tissue. However, recent evidence indicates that the formation of calcific vesicles in vascular tissue follows distinct cellular pathways compared to those in bone. Interestingly, clinicians have observed an unexplained phenomenon connecting the incidence of both types of calcification in patients, termed the calcification paradox, in which loss of mineral in one tissue correlates with increased mineral content in the other. However, the mechanisms underlying the calcification paradox remain unclear.

Materials and

Methods: : In this study, we performed an unbiased analysis of the lipid and protein composition of osteogenic treated VSMCs in vitro to identify key factors that contribute to pathological mineralization. Osteoblasts (OBs) —the primary cell type responsible for bone calcification—were similarly treated and analyzed to further explore the differences in these parallel but distinct cellular processes.

Results, Conclusions, and Discussions:: Our preliminary results indicate that vascular and bone derived cells indeed utilize different profiles of lipids and up-regulate unique vesicular proteins throughout mineralization. This highlights their distinct underlying cellular pathways for the release of calcific extracellular vesicles and the need to improve our understanding of these processes to guide treatment development.

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