Abstract 517: The CYP4A-20-HETE System Regulation of Endothelial Progenitor Cell Functions that Associated with Angiogenesis

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Li Chen ◽  
Alexander Braverman ◽  
Frank Zhang ◽  
John Falck ◽  
Ali Syed Arbab ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Vascular Effects ◽  
Endothelial Progenitor ◽  
Cell Functions ◽  
And Migration ◽  
Synthase Inhibitor ◽  
Proliferation And Migration

The CYP4A-20-HETE system regulates the neovascularization process via its potent vascular effects mainly on endothelial cells and vascular smooth muscle cells. Endothelial progenitor cells (EPC) also actively participate in physiological and pathological neovascularization. Our group first reported that the CYP4A-20-HETE system is present and functional in EPC derived from human umbilical cord blood (HUCB) and that EPC also respond to exogenous 20-HETE with increased proliferation and migration. We hypothesized that the angiogenic actions of the CYP4A-20-HETE system may involve regulation of EPC functions that associated with angiogenesis. In this study, we identified CYP4A11/22 as the main 20-HETE synthases in EPC derived from HUCB by real time PCR. We also examined the effects of exogenous 20-HETE on EPC adhesion since adhesion of EPC to extracellular matrix is an important aspect of EPC homing to the sites where angiogenesis is occurring. We found that 20-HETE (1 μM) increased EPC adhesion to fibronectin and SDF-1α coating by ∼40% and ∼35%, respectively. These increases in adhesion are completely abolished in the presence of 20-hydroxy-6, 15-eicosadienoic acid (20-HEDE), a 20-HETE antagonist. We further established the mouse ischemic hindlimb model to study the effects of pharmacological inhibition of the CYP4A/F-20-HETE system using the 20-HETE synthase inhibitor Dibromo-dodecenyl-methylsulfimide (DDMS) and 20-HEDE on compensatory angiogenesis in response to ischemia. Systemic treatment of animals with 10 mg/kg/day of either DDMS or 20-HEDE inhibited hindlimb compensatory angiogenesis by more than 50% without significant effects on the blood pressure. Specific targeting of the EPC-derived CYP4A-20-HETE system needs to be performed to further dissecting the role of systemic and EPC-derived 20-HETE on angiogenic processes. These findings implicates the CYP4A-20-HETE system as a novel regulator of EPC functions that are associated with angiogenesis and suggests that it can act as both an autocrine and paracrine regulatory factor.

scholarly journals Human umbilical cord blood-mesenchymal stem cell-derived secretome in combination with atorvastatin enhances endothelial progenitor cells proliferation and migration

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 537
Author(s):  
Yudi Her Oktaviono ◽  
Suryo Ardi Hutomo ◽  
Makhyan Jibril Al-Farabi ◽  
Angliana Chouw ◽  
Ferry Sandra
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
And Migration ◽  
Proliferation And Migration

Background: Human umbilical cord blood-mesenchymal stem cell (hUCB-MSC)-derived secretome is known to be able to promote neovascularization and angiogenesis, so it is also thought to have a capability to modulate endothelial progenitor cell (EPC) functions. Atorvastatin is the cornerstone of coronary artery disease (CAD) treatment which can enhance EPCs proliferation and migration. This study aims to analyze the effect of the hUCB-MSC-derived secretome and its combination with atorvastatin toward EPCs proliferation and migration. Methods: EPCs were isolated from a CAD patient’s peripheral blood. Cultured EPCs were divided into a control group and treatment group of 2.5 µM atorvastatin, hUCB-MSC-derived secretome (2%, 10%, and 20% concentration) and its combination. EPCs proliferation was evaluated using an MTT cell proliferation assay, and EPC migration was evaluated using a Transwell migration assay kit. Results: This research showed that hUCB-MSC-derived secretomes significantly increase EPC proliferation and migration in a dose-dependent manner. The high concentration of hUCB-MSC-derived secretome were shown to be superior to atorvastatin in inducing EPC proliferation and migration (p<0.001). A combination of the hUCB-MSC-derived secretome and atorvastatin shown to improve EPCs proliferation and migration compared to hUCB-MSC-derived secretome treatment or atorvastatin alone (p<0.001). Conclusions: This study concluded that the hUCB-MSC-derived secretome work synergistically with atorvastatin treatment in improving EPCs proliferation and migration.

scholarly journals Human umbilical cord blood-mesenchymal stem cell-derived secretome in combination with atorvastatin enhances endothelial progenitor cells proliferation and migration

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 537
Author(s):  
Yudi Her Oktaviono ◽  
Suryo Ardi Hutomo ◽  
Makhyan Jibril Al-Farabi ◽  
Angliana Chouw ◽  
Ferry Sandra
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
And Migration ◽  
Proliferation And Migration

Background: Human umbilical cord blood-mesenchymal stem cell (hUCB-MSC)-derived secretome is known to be able to promote neovascularization and angiogenesis, so it is also thought to have a capability to modulate endothelial progenitor cell (EPC) functions. Atorvastatin is the cornerstone of coronary artery disease (CAD) treatment which can enhance EPCs proliferation and migration. This study aims to analyze the effect of the hUCB-MSC-derived secretome and its combination with atorvastatin toward EPCs proliferation and migration. Methods: EPCs were isolated from a CAD patient’s peripheral blood. Cultured EPCs were divided into a control group and treatment group of 2.5 µM atorvastatin, hUCB-MSC-derived secretome (2%, 10%, and 20% concentration) and its combination. EPCs proliferation was evaluated using an MTT cell proliferation assay, and EPC migration was evaluated using a Transwell migration assay kit. Results: This research showed that hUCB-MSC-derived secretomes significantly increase EPC proliferation and migration in a dose-dependent manner. The high concentration of hUCB-MSC-derived secretome were shown to be superior to atorvastatin in inducing EPC proliferation and migration (p<0.001). A combination of the hUCB-MSC-derived secretome and atorvastatin shown to improve EPCs proliferation and migration compared to hUCB-MSC-derived secretome treatment or atorvastatin alone (p<0.001). Conclusions: This study concluded that the hUCB-MSC-derived secretome work synergistically with atorvastatin treatment in improving EPCs proliferation and migration.

Abstract 404: The Role of 20-HETE in the Regulation of Endothelial Progenitor Cell Stemness

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Gregory Joseph ◽  
Li Chen ◽  
John R Falck ◽  
Michal L Schwartzman ◽  
Austin M Guo
Keyword(s):  
Flow Cytometry ◽  
Progenitor Cells ◽  
Cell Population ◽  
Progenitor Cell ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Synthesis Inhibitor ◽  
Endothelial Progenitor

Objective: Endothelial progenitor cells (EPC) are known to contribute to neovascularization by producing various angiogenic cytokines, such as VEGF, at target sites. Factors that are capable of maintaining EPC stemness can in turn promote EPC self-renewal, thereby increasing their angiogenic functions. We recently identified the CYP4A-derived 20-HETE regulates some of the EPC pro-angiogenic properties (e.g. proliferation, migration) in vitro . In the present study, we further investigated the role of 20-HETE in the regulation of EPC stemness that are associated with their angiogenic functions. Methods: Human umbilical cord blood-derived EPC were isolated by magnetic cell sorting and cultured in an EPC enrichment media. LC/MS/MS was performed in cells harvested at various times during the EPC-EC differentiation process for 20-HETE production. Next, real-time PCR was used to assess the effects of 20-HETE (1 nM) on the expression of Oct4, Sox2, and NANOG, genes commonly associated with cell stemness. Flow cytometry was performed to quantify the population of progenitor vs differentiated EPC in the presence and absence of a 20-HETE synthesis inhibitor (DDMS; 10 μM) or a 20-HETE competitive antagonist (6, 15-20-HEDGE; 10 nM) in EPC cultures. Lastly, the effects of global increase in 20-HETE induction in vivo on bone marrow (BM)-derived EPC stemness were also examined using flow cytometry. Results: We found that differentiation of EPC to EC was associated with a time-dependent decrease in 20-HETE production. Exogenous 20-HETE significantly increased the expression of Oct4, Sox2, and NANOG by 1.5-, 2-, and 8.2-fold, respectively. DDMS and 6, 15-20-HEDGE decreased the number of progenitor cell population compared to vehicle-treated controls. In contrast, addition of 20-HETE increased the number of cell population expressing progenitor cell markers. Finally, BM-derived EPC from high 20-HETE production mice CYP4a12tg contained 50% more progenitor cells than EPC derived from control animals. Conclusion: These results implicate 20-HETE as a novel regulator of EPC stemness and an important player in the regulation of angiogenic responses that require the contribution of EPC.

scholarly journals Up-regulation of Grb2-associated binder 1 promotes hepatocyte growth factor induced endothelial progenitor cell proliferation and migration

2018 ◽  
Author(s):  
Qing Fan ◽  
Liyu Zhang ◽  
Wenjie Zhu ◽  
Sheng Xue ◽  
Yisheng Song ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Control Cell ◽  
Adaptor Protein ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
And Migration ◽  
Hepatocyte Growth ◽  
Proliferation And Migration

Objectives. Grb2-associated binder 1 (Gab1), a scaffolding adaptor protein, plays an important role in transmitting key signals that control cell growth, migration, and function from multiple tyrosine kinase receptors. This study was designed to investigate the influence of upregulation of Gab1 in endothelial progenitor cells (EPCs) stimulated with hepatocyte growth factor (HGF), and the underlying molecular mechanisms. Materials and Methods. EPCs isolated from human umbilical cord blood were identified and divided into four groups. EPCs in the Control group were cultured normally; those in the Control+HGF group were treated with HGF stimulation; those in the AD-Gab1 group were transfected with adenovirus containing the Gab1 gene but not treated with HGF stimulation; and, those in the AD-Gab1+HGF group were treated with both HGF stimulation and transfection with adenovirus containing the Gab1 gene. Subsequently, Gab1 expression and proliferation and migration ability were compared for EPCs grown under different conditions. Furthermore, we measured phosphorylation levels of three key proteins Gab1, SHP2 and ERK1/2. Results. The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups. Conclusions. Upregulation of Gab1 promoted HGF-induced EPC proliferation and migration. Mechanistically, HGF stimulated Gab1 tyrosine phosphorylation in EPCs, thus leading to activation of extracellular regulated MAP kinase 1/2, which is involved in proliferation and migration signaling.

scholarly journals Involvement of F-Actin in Chaperonin-Containing t-Complex 1 Beta Regulating Mouse Mesangial Cell Functions in a Glucose-Induction Cell Model

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Jin-Shuen Chen ◽  
Li-Chien Chang ◽  
Chia-Chao Wu ◽  
Lai-King Yeung ◽  
Yuh-Feng Lin
Keyword(s):  
Mesangial Cell ◽  
Cell Model ◽  
Cell Contraction ◽  
Small Interference Rna ◽  
Cell Functions ◽  
T Complex ◽  
Glucose Induction ◽  
And Migration ◽  
Proliferation And Migration

The aim of this study is to investigate the role of chaperonin-containing t-complex polypeptide 1 beta (CCT2) in the regulation of mouse mesangial cell (mMC) contraction, proliferation, and migration with filamentous/globular-(F/G-) actin ratio under high glucose induction. A low CCT2 mMC model induced by treatment of small interference RNA was established. Groups with and without low CCT2 induction examined in normal and high (H) glucose conditions revealed the following major results: (1) low CCT2 or H glucose showed the ability to attenuate F/G-actin ratio; (2) groups with low F/G-actin ratio all showed less cell contraction; (3) suppression of CCT2 may reduce the proliferation and migration which were originally induced by H glucose. In conclusion, CCT2 can be used as a specific regulator for mMC contraction, proliferation, and migration affected by glucose, which mechanism may involve the alteration of F-actin, particularly for cell contraction.

scholarly journals Up-regulation of Grb2-associated binder 1 promotes hepatocyte growth factor-induced endothelial progenitor cell proliferation and migration

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6675
Author(s):  
Qing Fan ◽  
Liyu Zhang ◽  
Wenjie Zhu ◽  
Sheng Xue ◽  
Yisheng Song ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adaptor Protein ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
And Migration ◽  
Hepatocyte Growth ◽  
Proliferation And Migration

Objectives Grb2-associated binder 1 (Gab1), a scaffolding adaptor protein, plays an important role in transmitting key signals that control cell growth, migration, and function from multiple tyrosine kinase receptors. This study was designed to investigate the influence of upregulation of Gab1 in endothelial progenitor cells (EPCs) stimulated with hepatocyte growth factor (HGF), and the underlying molecular mechanisms. Materials and Methods Endothelial progenitor cells isolated from human umbilical cord blood were identified and divided into four groups. EPCs in the Control group were cultured normally; those in the Control+HGF group were treated with HGF stimulation; those in the AD-Gab1 group were transfected with adenovirus containing the Gab1 gene but not treated with HGF stimulation; and, those in the AD-Gab1+HGF group were treated with both HGF stimulation and transfection with adenovirus containing the Gab1 gene. Subsequently, Gab1 expression and proliferation and migration ability were compared for EPCs grown under different conditions. Furthermore, we measured phosphorylation levels of three key proteins Gab1, SHP2, and ERK1/2. Results The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups. Conclusions Upregulation of Gab1 promoted HGF-induced EPC proliferation and migration. Mechanistically, HGF stimulated Gab1 tyrosine phosphorylation in EPCs, thus leading to activation of extracellular regulated MAP kinase 1/2, which is involved in proliferation and migration signaling.

scholarly journals Up-regulation of Grb2-associated binder 1 promotes hepatocyte growth factor induced endothelial progenitor cell proliferation and migration

2018 ◽  
Author(s):  
Qing Fan ◽  
Liyu Zhang ◽  
Wenjie Zhu ◽  
Sheng Xue ◽  
Yisheng Song ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Control Cell ◽  
Adaptor Protein ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
And Migration ◽  
Hepatocyte Growth ◽  
Proliferation And Migration

Objectives. Grb2-associated binder 1 (Gab1), a scaffolding adaptor protein, plays an important role in transmitting key signals that control cell growth, migration, and function from multiple tyrosine kinase receptors. This study was designed to investigate the influence of upregulation of Gab1 in endothelial progenitor cells (EPCs) stimulated with hepatocyte growth factor (HGF), and the underlying molecular mechanisms. Materials and Methods. EPCs isolated from human umbilical cord blood were identified and divided into four groups. EPCs in the Control group were cultured normally; those in the Control+HGF group were treated with HGF stimulation; those in the AD-Gab1 group were transfected with adenovirus containing the Gab1 gene but not treated with HGF stimulation; and, those in the AD-Gab1+HGF group were treated with both HGF stimulation and transfection with adenovirus containing the Gab1 gene. Subsequently, Gab1 expression and proliferation and migration ability were compared for EPCs grown under different conditions. Furthermore, we measured phosphorylation levels of three key proteins Gab1, SHP2 and ERK1/2. Results. The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups. Conclusions. Upregulation of Gab1 promoted HGF-induced EPC proliferation and migration. Mechanistically, HGF stimulated Gab1 tyrosine phosphorylation in EPCs, thus leading to activation of extracellular regulated MAP kinase 1/2, which is involved in proliferation and migration signaling.

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