Neutel Cédric H G, Wesley Callan D, van Loo Cindy, Civati Céline, Mertens Freke, Zurek Michelle, Verhulst Anja, Pintelon Isabel, De Vos Winnok H, Spronck Bart, Roth Lynn, De Meyer Guido R Y, Martinet Wim, Guns Pieter-Jan
Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Commun Biol. 2024 Oct 2;7(1):1241. doi: 10.1038/s42003-024-06895-y.
Calciprotein particles (CPPs) are an endogenous buffering system, clearing excessive amounts of Ca and PO from the circulation and thereby preventing ectopic mineralization. CPPs circulate as primary CPPs (CPP1), which are small spherical colloidal particles, and can aggregate to form large, crystalline, secondary CPPs (CPP2). Even though it has been reported that CPPs are toxic to vascular smooth muscle cells (VSMC) in vitro, their effect(s) on the vasculature remain unclear. Here we have shown that CPP1, but not CPP2, increased arterial stiffness ex vivo. Interestingly, the effects were more pronounced in the abdominal infrarenal aorta compared to the thoracic descending aorta. Further, we demonstrated that CPP1 affected both endothelial and VSMC function, impairing vasorelaxation and contraction respectively. Concomitantly, arterial glycosaminoglycan accumulation was observed as well, which is indicative of an increased extracellular matrix stiffness. However, these effects were not observed in vivo. Hence, we concluded that CPP1 can induce vascular dysfunction.
钙蛋白颗粒（CPPs）是一种内源性缓冲系统，可清除循环中过量的钙和磷酸盐，从而防止异位矿化。CPPs以初级CPPs（CPP1）的形式循环，CPP1是小的球形胶体颗粒，可聚集形成大的结晶性次级CPPs（CPP2）。尽管有报道称CPPs在体外对血管平滑肌细胞（VSMC）有毒性，但其对血管系统的影响仍不清楚。在这里，我们已经表明，CPP1而非CPP2在体外增加了动脉僵硬度。有趣的是，与胸降主动脉相比，腹肾下主动脉的这种影响更为明显。此外，我们证明CPP1影响内皮细胞和VSMC功能，分别损害血管舒张和收缩。同时，还观察到动脉糖胺聚糖积累，这表明细胞外基质僵硬度增加。然而，在体内未观察到这些影响。因此，我们得出结论，CPP1可诱导血管功能障碍。
