Cardiology Division, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China.
Cardiology Division, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People's Republic of China.
Clin Interv Aging. 2022 Mar 17;17:287-294. doi: 10.2147/CIA.S337118. eCollection 2022.
Rheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis.
We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography.
Osteogenic EPCs OCN+CD34+KDR+ ( = 0.002) and OCN+CD34+ ( = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI -0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively).
Circulating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.
类风湿关节炎与骨代谢异常和血管老化加速有关，但缺乏两者之间的机制联系。本研究旨在探讨成骨细胞来源的循环内皮祖细胞（EPC）在血管老化中的作用，这种作用通过类风湿关节炎患者的动脉钙化来确定。
我们对 145 例连续的类风湿关节炎患者进行了流式细胞术研究，以确定成骨细胞来源的循环 OC 阳性（OCN+）CD34+KDR+和 OCN+CD34+与传统的早期 EPC CD34+CD133+KDR+的水平。通过非对比 CT（CT）和对比 CT 血管造影术评估胸主动脉（升主动脉和降主动脉）和颈动脉的总钙负荷。
成骨细胞 EPC OCN+CD34+KDR+（ = 0.002）和 OCN+CD34+（ = 0.001），以及年龄、高血压病史、收缩压、甘油三酯、HbA1c 和肌酐血清水平、来氟米特的使用和肱踝脉搏波速度（均<0.05），与主动脉和颈动脉钙化的簇状存在有关。多变量分析显示，循环 OCN+CD34+KDR+（B=14.4[95%CI 4.0 至 24.8]， =0.007）和 OCN+CD34+（B=9.6[95%CI 4.9 至 14.3]，<0.001）与主动脉钙负荷增加独立相关。OCN+CD34+EPC（B=0.8[95%CI 0.1 至 1.5]， =0.023），而不是 OCN+CD34+KDR+EPC（B=1.2[95%CI -0.2 至 2.6]，P=0.09），与颈动脉钙负荷进一步独立相关。相比之下，传统的早期 EPC CD34+CD133+KDR+与主动脉或颈动脉钙负荷无显著相关性（P=0.46 和 0.88）。
在类风湿关节炎患者中，循环成骨细胞来源的 EPC 水平与大动脉钙化所致的血管老化有关。这些发现可能提示骨骼-血管轴在风湿性疾病中的血管老化中起作用。需要进一步研究来描述这些观察结果的机制联系和基础。
