Clinical Interventions in Aging (Mar 2022)

Osteogenic Circulating Endothelial Progenitor Cells are Associated with Vascular Aging of the Large Arteries in Rheumatoid Arthritis

  • Chan YH,
  • Ngai MC,
  • Chen Y,
  • Wu MZ,
  • Yu YJ,
  • Zhen Z,
  • Lai K,
  • Chung HY,
  • Lau CS,
  • Tse HF,
  • Yiu KH

Journal volume & issue
Vol. Volume 17
pp. 287 – 294

Abstract

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Yap-Hang Chan,1 Michael Cheong Ngai,2 Yan Chen,1,3 Mei-Zhen Wu,1 Yu-Juan Yu,1 Zhe Zhen,1 Kevin Lai,1 Ho-Yin Chung,4 Chak-Sing Lau,4 Hung-Fat Tse,1,3 Kai-Hang Yiu1,3 1Cardiology Division, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 2Division of Hematology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 3Cardiology Division, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Division of Rheumatology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of ChinaCorrespondence: Kai-Hang Yiu, Cardiology Division, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, 1 Haiyuan 1st Road, Futian District, Shenzhen, 518053, Guangdong, People’s Republic of China, Tel +852 22553633, Fax +852 28186304, Email [email protected] and Aim: 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.Methods: 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.Results: Osteogenic EPCs OCN+CD34+KDR+ (P = 0.002) and OCN+CD34+ (P = 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 P < 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], P = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], P < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], P = 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).Conclusion: 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.Keywords: osteocalcin, endothelial progenitor cells, vascular aging, rheumatoid arthritis

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