Calciprotein Particles

Abstract

Hypercalcemia and hyperphosphatemia associate with an elevated risk of cardiovascular events, yet the pathophysiological basis of this association is unclear. Disturbed mineral homeostasis and the associated hypercalcemia and hyperphosphatemia may result in the formation of circulating calciprotein particles (CPPs) that aggregate the excessive calcium and phosphate ions. If not counteracted, the initially formed harmless amorphous spherical complexes (primary CPPs) may mature into damaging crystalline complexes (secondary CPPs). Secondary CPPs are internalized by vascular cells, causing a massive influx of calcium ions into the cytosol, leading to a proinflammatory response, cellular dysfunction, and cell death. Although the pathophysiological effects induced by CPPs in vascular cells receive increasing attention, a complete picture of how these particles contribute to the development of atherosclerosis and vascular calcification remains elusive. We here discuss existing knowledge on CPP formation and function in atherosclerosis and vascular calcification, techniques for investigating CPPs, and models currently applied to assess CPP-induced cardiovascular pathogenesis. Lastly, we evaluate the potential diagnostic value of serum CPP measurements and the therapeutic potential of anti-CPP therapies currently under development.

Calciprotein Particles Induce Endothelial Dysfunction by Impairing Endothelial Nitric Oxide Metabolism

“…Accelerated formation and ripening of secondary CPPs is associated with the development of VCs and progression of vascular diseases in patients with CKD. 11 Although the interaction between VSMCs and secondary CPPs during the development of VC has been extensively studied, the role of ECs in this process remains largely elusive. Here, we show for the first time that secondary CPPs hamper EC function by affecting the NO bioavailability and the NO metabolism.…”

“…[6][7][8] Recently, accelerated formation of secondary CPPs (ie, increased serum calcification propensity) has been associated with the development of accelerated VC in CKD. 8,10,11 A high calcification propensity, indicated by a shorter transition time (T 50 ) from primary to secondary CPPs, is associated with atherosclerotic vascular diseases and mortality in CKD patients (stage 2-4). 12 In addition, serum analysis of 200 CKD patients (stage 3-4) revealed that serum secondary CPP levels reflect a procalcific environment and can be linked to aortic stiffness.…”

“… 6 – 8 Recently, accelerated formation of secondary CPPs (ie, increased serum calcification propensity) has been associated with the development of accelerated VC in CKD. 8 , 10 , 11 …”

Multiscale Multimodal Characterization and Simulation of Structural Alterations in Failed Bioprosthetic Heart Valves

“…In contrast, the vast presence of the calcified particles both within and on the leaflet wall surface suggests a process of cellular origin (e.g. from macrophages or other cells, cell-derived structures or particles originating from the blood), as previously suggested (45)(46)(47)(48) for the same particles (same shape, size and composition) in native valves.…”

Complexity of Inflammation in the Trajectory of Vascular Disease: Interleukin 6 and Beyond

“…Cholesterol crystals are well known to activate NLRP3 in atherosclerotic foci, 4) but NLRP3 can be activated also by a number of damage-associated molecular patterns, including uric acid crystals 5) and calciprotein particles, 6) which are deposited in the arterial wall in lifestyle-related diseases. Two clinical trials have tested whether suppression of the NLRP3 inflammasome itself with colchicine can reduce the risk of cardiovascular events 7,8) : In COL-COT (Colchicine Cardiovascular Outcomes Trial), which was performed in patients soon after they had experienced a myocardial infarction, and LoDoCo2 (Low-Dose Colchicine 2), which was carried out in patients with coronary artery disease whose condition has been stable for at least 6 months, the addition of colchicine 0.5 mg/day to secondary prevention therapy further reduced the risk of cardiovascular events.…”