An investigation into the role of the CXCR7 chemokine receptor in acute myocardial infarction and angiogenesis

• Main Author: Taferner, Staša
• Format: Dissertation
• Language: English
• Published: UCL (University College London) 2019

Introduction: SDF-1α is a chemoattractant cytokine that can deliver both acute and chronic cardioprotective benefits to the heart. Although CXCR4 has been viewed as a main receptor for SDF-1α, a secondary receptor, CXCR7, has emerged as an important mediator of SDF-1α signalling. Interestingly, endothelial CXCR7 has been found to promote regeneration and ameliorate fibrosis in various tissues and organs; however, its exact role in ischaemic disease has yet to be determined. Therefore, we sought to examine the expression and function of CXCR7 in cardiovascular tissues, focusing on its potential as a novel cardioprotective strategy. Methods: RNAscope in situ hybridization, western blotting and flow cytometry were used to investigate expression and function of CXCR7 on endothelial cell lines, isolated mouse endothelial cells, and in the whole mouse heart. We examined CXCR7 downstream signalling pathways in presence and absence of CXCR7 agonists TC14012 and VUF11207 fumarate, as well as the effects of the CXCR7 agonists on endothelial cell migration and acute ischaemia-reperfusion injury. Results: CXCR7 is expressed in the adult mouse heart and in the endothelial cell lines MCEC and HUVEC. Most CXCR7 protein in the endothelial cells was observed to be intracellular under basal conditions. In line with this expression profile, exposure to CXCR7 agonists failed to activate cardioprotective protein kinases ERK1/2 and PI3K/Akt. Moreover, VUF11207 did not ameliorate acute ischaemia-reperfusion injury, whereas the role of both CXCR7 agonists in migration and angiogenesis is less clear. Conclusions: CXCR7 is expressed in the mouse vascular endothelium, but its role in activating cardioprotective signalling pathways, as well as its overall contribution to cardioprotection is unclear. Activation of the CXCR7 receptor does not appear to be a viable acute cardioprotective strategy in mice.