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Gene Expression Analysis of Endothelial Cells Exposed to Shear Stress Using Multiple Parallel-plate Flow Chambers
Published on: October 21, 2018
Shear stress improves the endothelial progenitor cell function via the CXCR7/ERK pathway axis in the coronary artery
Hua Zhou1, Qiang Tu2,3, Yan Zhang2
1Department of Medical Ultrasound, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
Insights
Shear stress enhances endothelial progenitor cell (EPC) function in Coronary Artery Disease (CAD) patients by upregulating the CXCR7/ERK pathway. This finding offers a new therapeutic target for improving EPC vasculogenic capacity in CAD.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Regenerative Medicine
Background:
- Endothelial progenitor cell (EPC) dysfunction is central to endothelial repair deficits in Coronary Artery Disease (CAD).
- Shear stress is known to benefit EPC function, but its specific impact on EPCs from CAD patients remains unclear.
- The CXCR7/ERK signaling pathway is implicated in regulating EPC function within the context of CAD.
Purpose of the Study:
- To investigate the effect of shear stress on EPC function in CAD patients.
- To elucidate the role of the CXCR7/ERK pathway in mediating shear stress-induced improvements in EPC function.
- To test the hypothesis that shear stress upregulates CXCR7/ERK signaling, thereby restoring EPC function in CAD.
Main Methods:
- Cultured EPCs from healthy adults and CAD patients.
- Utilized Lv-siRNA to knockdown CXCR7 in CAD-derived EPCs.
- Applied shear stress to CAD-derived EPCs using a biomimetic device.
- Assessed cell viability, migration, tube formation, and apoptosis.
- Analyzed CXCR7 and ERK pathway activation via Western blotting and qRT-PCR.
Main Results:
- CAD patient-derived EPCs exhibited reduced in vitro vasculogenic capacity and lower CXCR7/ERK pathway activation compared to healthy controls.
- Shear stress treatment significantly increased CXCR7 expression and ERK phosphorylation in CAD EPCs, enhancing their function.
- CXCR7 knockdown negated the beneficial effects of shear stress on EPC migration, adhesion, and tube formation.
Conclusions:
- Shear stress effectively upregulates the CXCR7/ERK pathway in EPCs from CAD patients.
- This upregulation restores and enhances the vasculogenic potential of CAD patient-derived EPCs.
- Targeting the CXCR7/ERK pathway with shear stress presents a promising therapeutic strategy for CAD treatment.
Background:
Dysfunction in the late Endothelial Progenitor Cells (EPCs) is responsible for endothelial repair in patients with Coronary Artery Disease (CAD), and the shear stress is beneficial for EPCs function. However, the impact of shear stress on the capacity of EPCs in CAD patients has not been elucidated yet. The C-X-C chemokine receptor 7/extracellular signal-regulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. Here, we hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients.
Methods:
The human Peripheral Blood Mononuclear Cells (PBMCs) were collected from healthy adults and CAD patients and then used for EPCs cultivation. The Lv-siRNA for human CXCR7 was transfected into induced EPCs isolated from the CAD patients. Meanwhile, the EPCs from CAD patients were subjected to shear stress generated by a biomimetic device. Next, the cell viability, migration, tube formation, and apoptosis were detected by CCK-8, Transwell assay, Matrigel, and flow cytometry, respectively. Also, the CXCR7/ERK pathways in human EPCs were analyzed by Western blotting and qRT-PCR.
Result:
Compared to the EPCs collected from normal adults, the CAD patient-derived EPCs showed reduced in vitro vasculogenic capacity. Also, the level of CXCR7 in CAD patient-derived EPCs was significantly reduced compared to the EPCs of healthy subjects. Meanwhile, the extracellular signal-regulated kinase (ERK), which represents a CXCR7 downstream signaling pathway, had decreased phosphorylation level. The shear stress treatment augmented the CXCR7 expression and also elevated ERK phosphorylation, which is comparable to the up-regulation of CAD patient-derived EPCs function. Further, the small interfering RNA (siRNA)-mediated CXCR7 knockdown diminished the enhanced migration, adhesion, and tube formation capacity of shear stress treated CAD patient-derived EPCs.
Conclusion:
Up-regulation of the CXCR7/ERK pathways by shear stress can be a promising new target in enhancing the vasculogenic ability of CAD patient-derived EPCs.
