Effects of insulin resistance on endothelial progenitor cells and vascular repair

2009 ◽  
Vol 117 (5) ◽  
pp. 173-190 ◽  
Author(s):  
Richard M. Cubbon ◽  
Matthew B. Kahn ◽  
Stephen B. Wheatcroft
Keyword(s):  
Insulin Resistance ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Damage ◽  
Glucose Disposal ◽  
No Production ◽  
Vascular Repair ◽  
Endothelial Progenitor ◽  
The Metabolic Syndrome ◽  
Underlying Mechanisms

Insulin resistance, a key feature of obesity, the metabolic syndrome and Type 2 diabetes mellitus, results in an array of metabolic and vascular phenomena which ultimately promote the development of atherosclerosis. Endothelial dysfunction is intricately related to insulin resistance through the parallel stimulatory effects of insulin on glucose disposal in metabolic tissues and NO production in the endothelium. Perturbations characteristic of insulin resistance, including dyslipidaemia, inflammation and oxidative stress, may jeopardize the structural or functional integrity of the endothelium. Recent evidence suggests that endothelial damage is mitigated by endogenous reparative processes which mediate endothelial regeneration. EPCs (endothelial progenitor cells) are circulating cells which have been identified as mediators of endothelial repair. Several of the abnormalities associated with insulin resistance, including reduced NO bioavailability, increased production of ROS (reactive oxygen species) and down-regulation of intracellular signalling pathways, have the potential to disrupt EPC function. Improvement in the number and function of EPCs may contribute to the protective actions of evidence-based therapies to reduce cardiometabolic risk. In the present article, we review the putative effects of insulin resistance on EPCs, discuss the underlying mechanisms and highlight potential therapeutic manoeuvres which could improve vascular repair in individuals with insulin resistance.

scholarly journals SAT0014 ENDOTHELIAL PROGENITOR CELLS: ROLE IN ENDOTHELIAL DAMAGE OF INTERSTITIAL LUNG DISEASE ASSOCIATED TO RHEUMATOID ARTHRITIS

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 ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Potential Role ◽  
Endothelial Damage ◽  
Research Support ◽  
Endothelial Progenitor

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

Effects of Fluid Shear Stress on eNOS mRNA Expression and NO Production in Human Endothelial Progenitor Cells

Cardiology ◽  
2006 ◽  
Vol 106 (2) ◽  
pp. 82-88 ◽  
Author(s):  
Jun Tao ◽  
Zhen Yang ◽  
Jie-Mei Wang ◽  
Chang Tu ◽  
Shi-Rong Pan
Keyword(s):  
Shear Stress ◽  
Mrna Expression ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Fluid Shear Stress ◽  
No Production ◽  
Fluid Shear ◽  
Endothelial Progenitor ◽  
Enos Mrna

Intrinsic Vascular Repair by Endothelial Progenitor Cells in Acute Coronary Syndromes: an Update Overview

2018 ◽  
Vol 15 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Vânia Leal ◽  
Carlos Fontes Ribeiro ◽  
Bárbara Oliveiros ◽  
Natália António ◽  
Sónia Silva
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Acute Coronary Syndromes ◽  
Vascular Repair ◽  
Endothelial Progenitor ◽  
Coronary Syndromes

scholarly journals Decreased Count and Dysfunction of Circulating EPCs in Postmenopausal Hypercholesterolemic Females via Reducing NO Production

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Luo ◽  
Quan-Neng Yan ◽  
Wan-Zhou Wu ◽  
Fan-Yan Luo
Keyword(s):  
Endothelial Dysfunction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Therapeutic Strategy ◽  
No Production ◽  
Endothelial Progenitor ◽  
Endothelial Repair ◽  
Flow Mediated Dilatation ◽  
Premenopausal Female ◽  
And Function

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.

Endothelial Progenitor Cells for Vascular Repair

2010 ◽  
pp. 297-320
Author(s):  
Melissa A. Brown ◽  
Cindy S. Cheng ◽  
George A. Truskey
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Vascular Repair ◽  
Endothelial Progenitor

scholarly journals Rejuvenated Circulating Endothelial Progenitor Cells and Nitric Oxide in Premenopausal Women with Hyperhomocysteinemia

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Long Peng ◽  
Qianlin Gu ◽  
Zhenhua Huang ◽  
Lijin Zeng ◽  
Chang Chu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Premenopausal Women ◽  
Underlying Mechanism ◽  
No Production ◽  
Endothelial Progenitor ◽  
Repair Capacity ◽  
Circulating Endothelial Progenitor Cells

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

Determination of Circulating Endothelial Cells and Endothelial Progenitor Cells Using Multicolor Flow Cytometry in Patients with Thrombophilia

2019 ◽  
Vol 142 (2) ◽  
pp. 113-119
Author(s):  
Martin Řádek ◽  
Eva Babuňková ◽  
Martin Špaček ◽  
Tomáš Kvasnička ◽  
Jan Kvasnička
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
High Dose ◽  
Multicolor Flow Cytometry ◽  
Endothelial Progenitor ◽  
Identification And Quantification

Background/Aims: Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) have been described as markers of endothelial damage and dysfunction in several diseases, including deep venous thrombosis. Their role in patients with known thrombophilia has not yet been evaluated. Both EPCs and CECs represent extremely rare cell populations. Therefore, it is essential to use standardized methods for their identification and quantification. Methods: In this study, we used multicolor flow cytometry to analyze the number of EPCs and CECs in patients with thrombophilia with or without a history of thrombosis. Patients with hematological malignancies after high-dose chemotherapy and patients with acute myocardial infarction were used as positive controls. Results: EPC and CEC immunophenotypes were determined as CD45dim/–CD34+CD146+CD133+ and CD45dim/–CD34+CD146+CD133–, respectively. Increased levels of endothelial cells were observed in positive control groups. No significant changes in the number of EPCs or CECs were detected in patients with thrombophilia compared to healthy controls. Conclusion: Our optimized multicolor flow cytometry method allows unambiguous identification and quantification of endothelial cells in the peripheral blood. Our results support previous studies showing that elevated levels of CECs could serve as an indicator of endothelial injury or dysfunction. Normal levels of CECs or EPCs were found in patients with thrombophilia.

scholarly journals Elevated GTP Cyclohydrolase I Pathway in Endothelial Progenitor Cells of Overweight Premenopausal Women

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shaohong Wu ◽  
Hao He ◽  
Ge-Xiu Liu ◽  
Xiao-Peng Li ◽  
Shun Yao ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Premenopausal Women ◽  
Normal Weight ◽  
Female Group ◽  
No Production ◽  
Endothelial Progenitor ◽  
Endothelial Repair ◽  
Significant Difference

Background/Aims. Sexual differences exist in endothelial progenitor cells (EPCs), and various cardiovascular risk factors are associated with the preservation of endothelial function in premenopausal women. However, it is unclear whether differences in endothelial function and circulating EPCs exist between overweight premenopausal women and age-matched men. Methods. We compared EPC counting and functions in normal-weight and overweight premenopausal women and men, evaluated endothelial function in each group, and detected the expression of the guanosine triphosphate cyclohydrolase I (GTPCH I) pathway. Results. The number of EPCs was lower in the male group than in the female group, regardless of normal-weight or overweight status, and there was no significant difference between the different weight groups among females or males. Endothelial function and EPC migration and proliferation were preserved in overweight premenopausal women compared with overweight men as were nitric oxide (NO) levels in plasma and secreted by EPCs. Endothelial function, the circulating EPC population, and NO levels were not different between normal-weight and overweight premenopausal women. Flow-mediated dilatation was significantly correlated with EPC function, plasma NO levels, and EPC-secreted NO. Conclusions. This investigation provides the first evidence for sex-based differences in EPC activity and endothelial function in overweight middle-aged individuals; these differences are associated with alterations in NO production and may partly occur through downregulation of the GTPCH I pathway. The present results provide new insights into the mechanism underlying the preserved endothelial function in overweight premenopausal women and may uncover a potential therapeutic target for endothelial repair in overweight population.

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