Calciprotein particles disrupt autophagy in vascular endothelial cells and smooth muscle cells

Calciprotein particles (CPPs) act as buffers against mineral overload, but during prolonged mineral stress they convert from the small, amorphous CPP1 form into large, crystalline CPP2. This shift is associated with endothelial dysfunction and arterial stiffness. In this brief report, we assessed the impact of CPPs on autophagy, a key intracellular homeostatic process for maintaining (cardio)vascular health, in human aortic endothelial cells (HAoECs), human aortic smooth muscle cells (HAoSMCs), and murine eGFP-mRFP-LC3 vascular smooth muscle cells (VSMCs). In HAoECs, both CPP1 and CPP2 (100 μg/mL [Ca²⁺], 24 h) increased LC3-II levels and reduced autophagic flux. In contrast, HAoSMCs showed impaired flux only after exposure to CPP2. In murine VSMCs, CPP2 reduced autolysosome formation without affecting autophagosome numbers. Together, these findings indicate that CPPs interfere with lysosomal function and autophagic flux, with CPP2 exerting a stronger effect in smooth muscle cells. This supports a mechanistic link between chronic mineral stress and vascular disease and suggests that enhancing autophagy could potentially help counteract CPP-associated cardiovascular risk.