3045Role of osteogenic circulating endothelial progenitor cells in dissemination of large arterial calcification in rheumatoid arthritis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y.-H Chan ◽  
M C Ngai ◽  
Y Chen ◽  
M Z Wu ◽  
Y J Yu ◽  
...  

Abstract Background Rheumatoid arthritis is associated with both abnormal bone metabolism and atherogenesis but mechanistic links were missing. Aim This study aimed to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPC)s in the severity and dissemination of systemic 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+ were strikingly associated with the clustered presence of aortic and carotid calcification (P=0.002 and 0.001 respectively, Figure). 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). Conclusions Circulating level of osteogenic EPC is associated with promulgated aortic and carotid calcification in patients with rheumatoid arthritis, suggesting a potential mechanistic role of the bone-vascular axis in pro-atherogenicity of rheumatic diseases. Acknowledgement/Funding General Research Fund, Hong Kong Research Grants Council

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 937.1-937
Author(s):  
V. Pulito-Cueto ◽  
S. Remuzgo-Martínez ◽  
F. Genre ◽  
V. M. Mora-Cuesta ◽  
D. Iturbe Fernández ◽  
...  

Background:Interstitial lung disease (ILD) is one of the most significant comorbidities of rheumatoid arthritis (RA), increasing the mortality in these patients [1,2]. Although the pathogenesis of ILD associated to RA (RA-ILD+) remains poorly defined [1], it is known that vascular tissue plays a crucial role in lung physiology [3]. In this context, a population of cells termed endothelial progenitor cells (EPC) are involved in vasculogenesis and endothelial tissue repair [4]. Previous reports suggest the implication of EPC in different conditions such as RA and idiopathic pulmonary fibrosis (IPF), the most common and destructive ILD [5,6]. Nevertheless, little is known about their specific role in RA-ILD+.Objectives:The purpose of this study was to shed light on the potential role of EPC in endothelial damage in RA-ILD+.Methods:Peripheral venous blood was collected from a total of 68 individuals (18 with RA-ILD+, 17 with RA-ILD-, 19 with IPF and 14 healthy controls). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by the expression of surface antigens by flow cytometry. The combination of antibodies against the stem cell marker CD34, the immature progenitor marker CD133, the endothelial marker VEGF receptor 2 (CD309) and the common leukocyte antigen CD45 was used. EPC were considered as CD34+, CD45Low, CD309+and CD133+. All statistical analyses were performed using Prism software 5 (GraphPad).Results:EPC frequency was significantly increased in patients with RA-ILD+, RA-ILD-and IPF compared to controls (p=0.001, p=0.002, p< 0.0001, respectively). Nevertheless, patients with RA, both RA-ILD+and RA-ILD-, showed a lower frequency of EPC than those with IPF (p= 0.048, p= 0.006, respectively).Conclusion:Our results provide evidence for a potential role of EPC as a reparative compensatory mechanism related to endothelial damage in RA-ILD+, RA-ILD-and IPF patients. Interestingly, EPC frequency may help to establish a differential diagnostic between patients with IPF and those who have an underlying autoimmune disease (RA-ILD+).References:[1] J Clin Med 2019; 8: 2038;[2] Arthritis Rheumatol 2015; 67: 28-38;[3] Nat Protoc 2015; 10: 1697-1708;[4] Science 1997; 275: 964-966;[5] Rheumatology (Oxford) 2012; 51: 1775-1784;[6] Angiogenesis 2013; 16: 147-157.Acknowledgments:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: PI18/00042 (ISCIII-ERDF); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Sonia Fernández-Rozas: None declared, Leticia Lera-Gómez: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, David Merino: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Alfonso Corrales Speakers bureau: Abbvie, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD


2013 ◽  
Vol 61 (10) ◽  
pp. E1371
Author(s):  
Francesca Felice ◽  
Rossella Di Stefano ◽  
Stefano Pini ◽  
Gianfranco Mazzotta ◽  
Francesco M. Bovenzi ◽  
...  

Lung Cancer ◽  
2005 ◽  
Vol 49 ◽  
pp. S368-S369
Author(s):  
B. Dome ◽  
J. Timar ◽  
G. Ostoros ◽  
L. Meszaros ◽  
J. Dobos ◽  
...  

2019 ◽  
Vol 32 (3) ◽  
pp. 770
Author(s):  
AsmaaS Abo El-Yazeed ◽  
LailaM Montaser ◽  
AhmedA Sonbol ◽  
AhmedS EL-Gammal

2019 ◽  
Vol 392 (6) ◽  
pp. 669-683 ◽  
Author(s):  
Jolly Mounir William Labib ◽  
Sawsan Aboul-Fotouh ◽  
Mohamed Z. Habib ◽  
Mohamed Abd Elrahman Ahmed Mekawy ◽  
Kawthar A. Farrag ◽  
...  

2013 ◽  
Vol 325 (1-2) ◽  
pp. 90-99 ◽  
Author(s):  
E. Paczkowska ◽  
M. Gołąb-Janowska ◽  
A. Bajer-Czajkowska ◽  
A. Machalińska ◽  
P. Ustianowski ◽  
...  

2010 ◽  
Vol 37 (3) ◽  
pp. 529-535 ◽  
Author(s):  
KAI-HANG YIU ◽  
SILUN WANG ◽  
MO-YIN MOK ◽  
GAIK CHENG OOI ◽  
PEK-LAN KHONG ◽  
...  

Objective.Patients with rheumatoid arthritis (RA) are prone to premature atherosclerosis. We hypothesize that depletion of circulating endothelial progenitor cells (EPC) related to RA can contribute to the development of atherosclerosis.Methods.We studied coronary calcifications by multidetector computed tomography and their relationship with different subtypes of circulating EPC in 70 patients with RA and 35 age- and sex-matched controls (mean age 54.1 ± 10.2 yrs, 87% were women). The presence of coronary atherosclerosis was defined as an Agatston score ≥ 10. Four subpopulations of EPC were determined by flow cytometry on the basis of surface expression of CD34, CD133, and KDR antigen: CD34+, CD34/KDR+, CD133+, and CD133/KDR+ EPC, respectively.Results.Among those with RA, 15 patients (21%) had coronary atherosclerosis. The mean Agatston score was higher (61.8 ± 201.7 vs 0.14 ± 0.69; p = 0.01) and coronary atherosclerosis was more prevalent (21.4% vs 0%; p < 0.01) in patients with RA compared to controls. RA patients with coronary atherosclerosis were older (66.2 ± 6.9 vs 51.5 ± 16.2 yrs; p < 0.01), had higher prevalence of hypertension (46.7% vs 14.5%; p = 0.01), and had lower CD133/KDR+ (0.45% ± 0.28% vs 0.89% ± 0.81%; p < 0.01) and CD133+ EPC levels (0.74% ± 0.39% vs 1.22% ± 0.83%; p < 0.01), but similar CD34/KDR+ and CD34+ EPC levels (all p > 0.05) compared to those without. Multiple logistic regression revealed that older age (OR 1.25, 95% CI 1.10–1.41, p < 0.01) and lower CD133/KDR+ EPC (OR 0.07, 95% CI 0.00–0.97, p < 0.01) were independent predictors for coronary atherosclerosis in patients with RA.Conclusion.Our results demonstrated that RA patients with coronary atherosclerosis have significantly lower levels of CD133/KDR+ and CD133+ EPC than those without. In addition to older age, lower levels of circulating CD133/KDR+ EPC also predicted occurrence of coronary atherosclerosis in RA patients.


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