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- Title
Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression.
- Authors
Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana
- Abstract
Aims Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model,we haveshownthat advanced atherosclerosis regression occurswhenlipid lowering is used in combination with bone-marrowendothelial progenitor cell (EPC) treatment.However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Methods and results ChemokinesCXCL1andCX3CL1were detected in the vascularwall of atheroregressingReversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1-CXCR2 and CX3CL1-CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression.We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. Conclusion CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis.
- Subjects
CHEMOKINE receptors; HEMATOPOIETIC stem cells; ATHEROSCLEROTIC plaque; ATHEROSCLEROSIS complications; MYOCARDIAL infarction; LABORATORY mice; THERAPEUTICS
- Publication
Cardiovascular Research, 2015, Vol 106, Issue 2, p324
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvv111