Lupus-prone New Zealand Black/New Zealand White F1 mice display endothelial dysfunction and abnormal phenotype and function of endothelial progenitor cells

Endothelial progenitor cells (EPCs) contribute to the endogenous endothelial repair program during hypercholesterolemia. EPC count and migratory and proliferative capacities remain unchanged in the premenopausal female with hypercholesterolemia. However, the changes of count and activity of circulating EPCs in the hypercholesterolemic postmenopausal females are unknown. Here, we find that the migratory and proliferative capacities of circulating EPCs were decreased in patients with hypercholesterolemia versus normocholesterolemia. No significant differences were found between postmenopausal females and age-matched males. NO production showed positive correlation with the activity and count of circulating EPCs in patients with hypercholesterolemia. Flow-mediated dilatation (FMD) is directly interrelated with EPC counts and function. Our findings reveal that decreased EPC count and endothelial dysfunction lead to less NO production in hypercholesterolemic postmenopausal females. Maintaining the EPC numbers and activity might be emerging as a potential therapeutic strategy to reduce the risk of cardiovascular injury in elder women.

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Regulatory effect of dimethylarginine dimethylaminohydrolase on endothelial progenitor cells differentiation and function

Cell Biology International ◽

10.1042/cbi034s042b ◽

2010 ◽

Vol 34 (8) ◽

pp. S42-S42

Author(s):

Qiong Yuan ◽

Chang‑Ping Hu ◽

Si‑Yu Liu ◽

Xu‑Meng Chen ◽

Jun Peng ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Regulatory Effect ◽

Dimethylarginine Dimethylaminohydrolase ◽

Endothelial Progenitor ◽

And Function

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Quantitative and functional evaluation of endothelial progenitor cells in patients with cardiac amyloidosis

European Heart Journal ◽

10.1093/ehjci/ehaa946.2114 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

O Itzhaki Ben Zadok ◽

D Leshem-Lev ◽

T Ben-Gal ◽

A Hamdan ◽

N Schamroth-Pravda ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Mtt Assay ◽

Cardiac Amyloidosis ◽

Microvascular Dysfunction ◽

Functional Evaluation ◽

Endothelial Progenitor ◽

Colony Forming Units ◽

Study Population ◽

And Function

Abstract Background Endothelial microvascular dysfunction is a known mechanism of injury in cardiac amyloidosis (CA), but evidence regarding the level and function of endothelial progenitor cells (EPCs) in patients with CA is lacking. Methods Study population included patients with light-chain or transthyretin (ATTR) CA. Patients with diagnosed heart failure and preserved ejection fraction (HFpEF) without monoclonal gammopathy and a 99mTc-DPD scan incompatible with TTR were used as controls. Blood circulating EPCs were assessed quantitatively by the expression of VEGFR-2(+), CD34(+) and CD133(+) using flow cytometry, and functionally by the formation of colony forming units (CFUs). MTT assay was used to demonstrate cell viability. Tests were repeated 3 months following the initiation of amyloid-suppressive therapies (either ATTR-stabilizer or targeted chemotherapy) in CA patients. Results Our preliminary cohort included 14 CA patients (median age 74 years, 62% ATTR CA). Patients with CA vs. patients with HFpEF (n=8) demonstrated lower expression of CD34(+)/VEGFR-2(+) cells [0.51% (IQR 0.4, 0.7) vs. 1.03% (IQR 0.6, 1.4), P=0.043] and CD133(+)/VEGFR-2(+) cells [0.35% (IQR 0.23, 0.52) to 1.07% (IQR 0.6, 1.5), P=0.003]. Functionally, no differences were noted between groups. Following the initiation of amyloid-suppressive therapies in CA patients, we observed the up-regulation of CD34(+)/VEGFR-2(+) cells [2.47% (IQR 2.1, 2.7), P<0.001] and CD133(+)/VEGFR-2(+) cells [1.38% (IQR 1.1, 1.7), P=0.003]. Moreover, functionally, active EPCs were evident microscopically by their ability to form colonies (from 0.5 CFUs [IQR 0, 1.5) to 2 CFUs (IQR 1, 3.5), P=0.023]. EPCs' viability was demonstrated by an MTT assay [0.12 (IQR 0.04, 0.12) to 0.24 (IQR 0.16, 0.3), p=0.014]. Conclusions These preliminary results demonstrate reduced EPCs levels in CA patients indicating significant microvascular impairment. Amyloid-targeted therapies induce the activation of EPCs, thus possibly promoting endothelial regeneration. These findings may represent a novel mechanism of action of amyloid-suppressive therapies EPCs in CA patients and during therapy Funding Acknowledgement Type of funding source: None

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Bone Marrow-Derived Endothelial Progenitor Cells: A Promising Therapeutic Alternative for Corneal Endothelial Dysfunction

Cells Tissues Organs ◽

10.1159/000319797 ◽

2011 ◽

Vol 193 (4) ◽

pp. 253-263 ◽

Cited By ~ 31

Author(s):

Chunyi Shao ◽

Yao Fu ◽

Wenjuan Lu ◽

Xianqun Fan

Keyword(s):

Bone Marrow ◽

Endothelial Dysfunction ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor ◽

Therapeutic Alternative ◽

Corneal Endothelial Dysfunction

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Correction: Period2 Deficiency Blunts Hypoxia-Induced Mobilization and Function of Endothelial Progenitor Cells

PLoS ONE ◽

10.1371/journal.pone.0119196 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0119196

Author(s):

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor ◽

And Function

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Abstract 3698: Decreased Circulating Endothelial Progenitor Cells and Endothelial Dysfunction: a Novel Mechanism of Atherogenesis in Obesity.

Circulation ◽

10.1161/circ.116.suppl_16.ii_839-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Paulo F Leite ◽

Claudia R Andrade ◽

Santa Poppe ◽

Luiz A Cesar ◽

Silmara Coimbra ◽

...

Keyword(s):

Metabolic Syndrome ◽

Multivariate Analysis ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Obese Patients ◽

Endothelial Progenitor ◽

Circulating Endothelial Progenitor Cells ◽

Morbid Obese

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.

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