AIMS Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with the development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with the presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggravate VC and vascular dysfunction in vivo are currently lacking. Here, we assessed the overall burden of abdominal VC in healthy kidney donors and CKD patients and subsequently performed transcriptome profiling in the vascular tissue obtained from these subjects, linking outcome to CPP counts and calcification propensity. METHODS AND RESULTS Calcification scores were quantified in renal arteries, iliac arteries, and abdominal aorta using computed tomography (CT) scans of kidney donors and CKD patients. The vascular tissue was collected from kidney donors (renal artery) and CKD patients (iliac artery), after which bulk RNA sequencing and gene set enrichment analysis (GSEA) were performed on a subset of patients. Calcification propensity (crystallization time, T50) was measured using nephelometry and CPP counts with microparticle flow cytometric analysis. Increased calcification scores (based on CT) were found in CKD patients compared to kidney donors. Transcriptome profiling revealed enrichment for processes related to endothelial activation, inflammation, extracellular matrix (ECM) remodelling, and ossification in CKD vascular biopsies compared to kidney donors. Calcification propensity was increased in CKD, as well as CPP counts, with the latter being significantly associated with markers of vascular remodelling. CONCLUSION Our findings reveal that CKD is characterized by systemic VC with increased calcification propensity and CPP counts. Transcriptome profiling showed altered vascular gene expression with enrichment for endothelial activation, inflammation, ECM remodelling, and ossification. Moreover, we demonstrate, for the first time, that vascular remodelling processes are associated with increased circulating CPP counts. Interventions targeting CPPs are promising avenues for alleviating vascular remodelling and VC in CKD.

中文翻译：

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钙蛋白颗粒计数与慢性肾病中的血管重塑有关。


AIMS 钙蛋白颗粒 （CPP） 是与慢性肾脏病 （CKD） 中血管钙化 （VC） 发展相关的循环钙和磷酸盐纳米颗粒。尽管最近的研究一直集中在 CPPs 与 CKD 中 VC 存在的关联上，但目前缺乏对 CPPs 可能加重体内 VC 和血管功能障碍的潜在过程和机制的见解。在这里，我们评估了健康肾脏供体和 CKD 患者腹部 VC 的总体负担，随后对从这些受试者获得的血管组织中进行了转录组分析，将结果与 CPP 计数和钙化倾向联系起来。方法和结果 使用肾脏供体和 CKD 患者的计算机断层扫描 （CT） 扫描量化肾动脉、髂动脉和腹主动脉的钙化评分。从肾脏供体 （肾动脉） 和 CKD 患者 （髂动脉） 收集血管组织，然后对一部分患者进行批量 RNA 测序和基因集富集分析 （GSEA）。使用比浊法和 CPP 计数结合微粒流式细胞术分析测量钙化倾向 （结晶时间，T50）。与肾脏供体相比，CKD 患者的钙化评分 （基于 CT） 增加。转录组分析显示，与肾脏供体相比，CKD 血管活检中与内皮活化、炎症、细胞外基质 （ECM） 重塑和骨化相关的过程富集。CKD 和 CPP 计数的钙化倾向增加，后者与血管重塑标志物显著相关。 结论 我们的研究结果显示，CKD 的特征是全身性 VC 伴有钙化倾向和 CPP 计数增加。转录组分析显示血管基因表达改变，内皮活化、炎症、ECM 重塑和骨化富集。此外，我们首次证明血管重塑过程与循环 CPP 计数增加有关。针对 CPP 的干预措施是缓解 CKD 血管重塑和 VC 的有前途的途径。