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Updated: Mar 15, 2026
In Vitro Model of Coronary Angiogenesis
Published on: March 10, 2020
CXCR7/p-ERK-Signaling Is a Novel Target for Therapeutic Vasculogenesis in Patients with Coronary Artery Disease
Zheng Cao1, Xinzhu Tong1,2, Wenhao Xia2
1Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
Insights
CXC chemokine receptor 7 (CXCR7) signaling is crucial for endothelial outgrowth cells (EOCs) in coronary artery disease (CAD). Upregulating CXCR7 improves EOC vasculogenic capacity, suggesting it as a potential therapeutic target for CAD.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Regenerative Medicine
Background:
- Coronary artery disease (CAD) involves impaired vasculogenesis due to endothelial outgrowth cell (EOC) dysfunction.
- CXC chemokine receptor 7 (CXCR7) regulates EOC neovascularization, but its role in CAD is unclear.
Purpose of the Study:
- To investigate EOC vasculogenic capacity alterations in CAD patients.
- To elucidate the mechanism involving CXCR7 and its downstream signaling in CAD vasculogenesis.
Main Methods:
- Compared EOCs from CAD patients and healthy subjects in vitro.
- Assessed CXCR7 expression and extracellular signal-regulated kinase (ERK) phosphorylation.
- Utilized adenovirus for CXCR7 introduction and siRNA/inhibitors for pathway blockade.
Main Results:
- CAD EOCs exhibited impaired vasculogenic function and downregulated CXCR7 expression.
- ERK phosphorylation was reduced in CAD EOCs, correlating with CXCR7 levels.
- Adenovirus-mediated CXCR7 upregulation enhanced EOC function and ERK phosphorylation.
- siRNA against CXCR7 and ERK inhibition blocked EOC adhesion and vasculogenesis.
Conclusions:
- Downregulated CXCR7 signaling impairs EOC vasculogenic capacity in CAD patients.
- Upregulating CXCR7 signaling enhances EOC function, offering a potential therapeutic strategy for CAD.
Abstract:
Coronary artery disease (CAD) is characterized by insufficient vasculogenic response to ischemia, which is typically accompanied by dysfunction of endothelial outgrowth cells (EOCs). CXC chemokine receptor 7 (CXCR7) is a key modulator of the neovascularization of EOCs to perfusion defect area. However, the mechanism underlying the role of EOCs in CAD-related abnormal vasculogenesis is still not clear. Here, we investigated the alteration of EOCs-related vasculogenic capacity in patients with CAD and its potential mechanism. Compared with EOCs isolated from healthy subjects, EOCs from CAD patients showed an impaired vasculogenic function in vitro. CXCR7 expression of EOCs from CAD patients was downregulated. Meanwhile, the phosphorylation of extracellular signal-regulated kinase (ERK), downstream of CXCR7 signaling, was also reduced. CXCR7 expression introduced by adenovirus increased the phosphorylation of ERK, which was parallel to improved function of EOCs. The enhanced adhesion and vasculogenesis of EOCs can be blocked by short interfering RNA (siRNA) against CXCR7 and ERK inhibitor PD098059. Therefore, our study demonstrates that the upregulation of CXCR7 signaling contributes to increased vasculogenic capacity of EOCs from CAD patients, indicating that CXCR7 signaling may be a novel therapeutic vasculogenic target for CAD.
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