Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression
Abstract
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 have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial 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. Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa 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 ath...Continue Reading
References
Citations
Related Concepts
Related Feeds
Carotid Artery Diseases
Carotid artery disease is a group of pathological conditions of the carotid artery. Discover the latest research on carotid artery disease here.
Anxiety Disorders
Discover the latest research on anxiety disorders including agoraphobia, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder here.
Atherosclerosis Disease Progression
Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.