Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic conduction abnormalities in rheumatic patients

Chan, Yap‐Hang; Ngai, Cheong; Chen, Yan; Wu, Mei‐Zhen; Yu, Yu-Juan; Zhen, Zhe; Lai, Kevin; Cheung, Tik Shing; Ho, Lok Sang; Chung, Ho Yin; Lau, Chak‐Sing; Lau, Chu‐Pak; Tse, Hung‐Fat; Yiu, Kai‐Hang

doi:10.1111/anec.12651

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…While circulating endothelial progenitor cells (EPC) were believed to generally play a protective role in ameliorating vascular insults by homing to sites of vascular injury and promoting re-endothelialization, 1 recent studies revealed that sub-progenies of EPC that express the osteoblastic marker, namely osteocalcin (OCN), could have detrimental effects in promoting cardiovascular calcification and aging. 2–4 …”

Section: Introductionmentioning

confidence: 99%

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

Chan

Ngai

Chen

et al. 2022

CIA

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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.

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Section: Introductionmentioning

confidence: 99%

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

Chan

Ngai

Chen

et al. 2022

CIA

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Cumulative Rheumatic Inflammation Modulates the Bone–Vascular Axis and Risk of Coronary Calcification

Chan

Ngai

Chen

et al. 2019

JAHA

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Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time‐adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C‐reactive protein over 60 months immediately preceding computed tomography coronary angiography. Flow cytometry was performed to measure the osteocalcin‐positive ( OCN + ) CD 34 + KDR + and OCN + CD 34 + circulating endothelial progenitor cells ( EPCs ). Conventional early circulating EPCs CD 34 + CD 133 + KDR + was determined. Coronary calcification was defined as any Agatston score >0. 50% of patients (n=72/145) had coronary calcification. CRI score was associated with presence of coronary calcification ( P =0.004) (multivariable‐adjusted: highest versus lowest quartile: odds ratio=5.6 [95% CI 1.1–28.9], P =0.041). Receiver operating characteristics curve revealed divergent behavior of OCN ‐expressing circulating EPCs ( OCN + CD 34 + EPCs : area under the curve=0.60, P =0.034; OCN + CD 34 + KDR + EPCs : area under the curve=0.59, P =0.053, positive predictors) versus conventional early EPCs ( CD 34 + CD 133 + KDR + : area under the curve=0.60, P =0.034, negative predictor) for coronary calcification, which persisted after multivariable adjustments ( OCN + CD 34 + KDR + [>75th percentile]: odds ratio=7.2 [95% CI 1.8–27.9], P =0.005; OCN + CD 34 + EPCs [>75th percentile]: odds ratio=6.0 [95% CI 1.5–23.3], P =...

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Endothelial Progenitor Cells and Rheumatoid Arthritis: Response to Endothelial Dysfunction and Clinical Evidences

Komici

Perna

Rocca

et al. 2021

IJMS

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Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the swelling of multiple joints, pain and stiffness, and accelerated atherosclerosis. Sustained immune response and chronic inflammation, which characterize RA, may induce endothelial activation, damage and dysfunction. An equilibrium between endothelial damage and repair, together with the preservation of endothelial integrity, is of crucial importance for the homeostasis of endothelium. Endothelial Progenitor Cells (EPCs) represent a heterogenous cell population, characterized by the ability to differentiate into mature endothelial cells (ECs), which contribute to vascular homeostasis, neovascularization and endothelial repair. A modification of the number and function of EPCs has been described in numerous chronic inflammatory and auto-immune conditions; however, reports that focus on the number and functions of EPCs in RA are characterized by conflicting results, and discrepancies exist among different studies. In the present review, the authors describe EPCs’ role and response to RA-related endothelial modification, with the aim of illustrating current evidence regarding the level of EPCs and their function in this disease, to summarize EPCs’ role as a biomarker in cardiovascular comorbidities related to RA, and finally, to discuss the modulation of EPCs secondary to RA therapy.

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Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic conduction abnormalities in rheumatic patients

Cited by 3 publications

References 29 publications

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

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

Cumulative Rheumatic Inflammation Modulates the Bone–Vascular Axis and Risk of Coronary Calcification

Endothelial Progenitor Cells and Rheumatoid Arthritis: Response to Endothelial Dysfunction and Clinical Evidences

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