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. 2022 Mar 17:17:287-294.
doi: 10.2147/CIA.S337118. eCollection 2022.

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

Yap-Hang Chan  1   2 , Michael Cheong Ngai  3 , Yan Chen  1   2 , Mei-Zhen Wu  2 , Yu-Juan Yu  2 , Zhe Zhen  2 , Kevin Lai  2 , Ho-Yin Chung  4 , Chak-Sing Lau  4 , Hung-Fat Tse  1   2 , Kai-Hang Yiu  1   2
Affiliations

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

Yap-Hang Chan et al. Clin Interv Aging. .

Abstract

Background 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: endothelial progenitor cells; osteocalcin; rheumatoid arthritis; vascular aging.

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Conflict of interest statement

The authors declared no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Osteogenic OCN+ CD34+KDR+/OCN+CD34+ circulating EPCs and phenotype profile of vascular aging (*P<0.05).
See this image and copyright information in PMC

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