scholarly journals Bone Erosion Is Associated With Reduction of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Rheumatoid Arthritis

2014 ◽  
Vol 66 (6) ◽  
pp. 1450-1460 ◽  
Author(s):  
Yune-Jung Park ◽  
Ji-Young Kim ◽  
Jeongmi Park ◽  
Jin-Jung Choi ◽  
Wan-Uk Kim ◽  
...  
Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paulo F Leite ◽  
Claudia R Andrade ◽  
Santa Poppe ◽  
Luiz A Cesar ◽  
Silmara Coimbra ◽  
...  

Underlying mechanisms of endothelial dysfunction in obesity are not fully understood. Circulating Endothelial Progenitor Cells (EPCs) are known to promote endothelial repair. Our aim was to assess the number/function of EPCs in morbid obese individuals and its correlation with endothelial function and inflammatory markers. EPCs were isolated from 33 morbid obese patients (age 47±1.8 y; men=34%; BMI=49±2.1 kg/m 2 , metabolic syndrome=84%) and 20 lean controls. Peripheral blood EPC number was significantly reduced in obese patients both with flow cytometry (KDR + /CD34 + ; 0.041±0.04 vs 0.074±0.05 %events, p<0.001) and fluorescence analysis after short-term culture (49±4 vs 28±2 cells/field, p<0.001). The plasma number of primitive CD 133 + cells, and concentrations of VEGF (Elisa) and nitrogen oxides (which potentially recruit EPCs), were similar to control, suggesting that reduction of EPCs occurs distally to early cell differentiation. Importantly, C-Reactive Protein (CRP), robustly increased in obese patients (0.15±0.04 vs 1.3±0.3; p=0.003), was a strong predictor of reduced EPC number at multivariate analysis (r=0.623; p < 0.001). Likewise, the migratory response of EPCs to VEGF in vitro was significantly impaired in obese vs controls, despite similar VEGF receptor numbers. Multivariate analysis suggested potential roles of metabolic syndrome and leptin in such effect. Endothelial function at flow-mediated brachial artery reactivity was markedly reduced (by 60%) in obese patients, and had a significant inverse correlation with EPC number (r= 0.678; p< 0.001). Carotid intimal thickness was also increased in obese patients (0.68±0.02 vs 0.58±0.08; p=0.001). On the other hand, the number of circulating endothelial cells (CD31 + /CD106 + ) was similar in both groups, suggesting that apoptosis was not enhanced in the obese. These results suggest for the first time that reduced number and migratory capacity of EPCs correlate with endothelial dysfunction or increased CRP and may be a key underlying mechanism of vascular complications and atherosclerosis in obesity.


Stroke ◽  
2008 ◽  
Vol 39 (5) ◽  
pp. 1441-1447 ◽  
Author(s):  
Kon Chu ◽  
Keun-Hwa Jung ◽  
Soon-Tae Lee ◽  
Hee-Kwon Park ◽  
Dong-In Sinn ◽  
...  

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


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.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hua Chen ◽  
Jianati Qiuwaxi ◽  
Ching-Yuen Wong ◽  
Sheung-Wai Li ◽  
Hiu-Ting Chan ◽  
...  

Introduction: Although the mechanisms remain unclear, depression is associated with endothelial dysfunction and increases risk of cardiovascular disease (CVD). Recent studies suggest that circulating endothelial progenitor cells (EPC) play an important role in endothelial repair and correlate with endothelial function. Hypothesis: We assessed the hypothesis that the presence of depressive symptoms in subjects without significant CVD is associated with depletion of circulating EPC and impaired endothelial function. Methods: We studied the relationship between the level of circulating EPCs, endothelial function and depression status in 129 healthy normal individuals (54±10 yrs, 54 men) without prior CVD or diabetes. The numbers of circulating CD34/KDR + EPCs were determined by flow cytometry, and the depression status was estimated by Depression Anxiety Stress Scales. Brachial artery flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound imaging. Results: The median depression score of the study population was 4 (range 0 to 34), and 41 subjects (32 %) had high depression score (DS) ≥8 (defined by ≥ the 75th percentile of the depression score). There were no significant differences in baseline clinical characteristics between subjects with or without high DS (all P > 0.05 ). However, subjects with high DS had significantly lower FMD (5.4±2.7 vs. 8.0±4.0 %, P < 0.001 ) and CD34/KDR + EPC% (1.24±1.27 vs. 2.02±2.43 %, P = 0.037 ) than those with normal DS. Multivariate regression analysis revealed that a high DS (OR 1.08, 95%CI: 1.02–1.15, P = 0.009 ) and old age (OR 1.05, 95%CI: 1.01–1.09, P = 0.029 ) were independent predictors for decreased FMD. Conclusions: The results of this study demonstrated that in subjects without significant CVD, the presence of a high DS was associated with impaired brachial FMD and depletion of circulating EPC. Nevertheless, only depression score, but not the percentage of circulating EPC significantly correlated brachial FMD, and was an independent predictor for impaired brachial FMD.


Life Sciences ◽  
2006 ◽  
Vol 79 (25) ◽  
pp. 2364-2369 ◽  
Author(s):  
Jacob N. Ablin ◽  
Viktoria Boguslavski ◽  
Valerie Aloush ◽  
Ori Elkayam ◽  
Daphna Paran ◽  
...  

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