Abstract
BackgroundDysfunction 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.MethodsThe 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.ResultCompared 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.ConclusionUp-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.
Highlights
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
The results suggested that shear stress significantly enhanced EPCs migration and adhesion capacity in CAD patients (Fig. 2a-b)
We found that 12 h of shear stress exposure in EPCs at 15-dyn/cm2 markedly up-regulated the CXC chemokine receptor 7 (CXCR7) expression at mRNA (Fig. 2d) and protein (Fig. 2e) levels
Summary
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. The C-X-C chemokine receptor 7/extracellular signalregulated kinase (CXCR7)/(ERK) pathways are identified to regulate EPCs function in CAD patients. We hypothesize that shear stress upregulates the CXCR7/ERK pathways, which restore the EPCs function in CAD patients. The EPCs function is impaired in CAD patients delaying the progression of vascular endothelial repair response [11,12,13]. It is necessary to identify a new way to improve the EPCs function in CAD patients and reduce the occurrence of CVDs. Shear stress is a measure of nonpharmacological intervention which benefits the vascular endothelial homeostasis [17,18,19]. Based on our previous study, impaired phosphorylation of the CXCR7-mediated extracellular signal-regulated kinase (ERK) pathway is involved in CADrelated decline of EPCs function in vitro [23]
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