The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury.
Tobias GetzinKashyap KrishnasamyJaba GamrekelashviliTamar KapanadzeAnne LimbourgChristine HägerL Christian NappJohann BauersachsHermann HallerSusanne V FleigPublished in: EMBO molecular medicine (2019)
Regeneration of arterial endothelium after injury is critical for the maintenance of normal blood flow, cell trafficking, and vascular function. Using mouse models of carotid injury, we show that the transition from a static to a dynamic phase of endothelial regeneration is marked by a strong increase in endothelial proliferation, which is accompanied by induction of the chemokine CX3CL1 in endothelial cells near the wound edge, leading to progressive recruitment of Ly6Clo monocytes expressing high levels of the cognate CX3CR1 chemokine receptor. In Cx3cr1-deficient mice recruitment of Ly6Clo monocytes, endothelial proliferation and regeneration of the endothelial monolayer after carotid injury are impaired, which is rescued by acute transfer of normal Ly6Clo monocytes. Furthermore, human non-classical monocytes induce proliferation of endothelial cells in co-culture experiments in a VEGFA-dependent manner, and monocyte transfer following carotid injury promotes endothelial wound closure in a hybrid mouse model in vivo Thus, CX3CR1 coordinates recruitment of specific monocyte subsets to sites of endothelial regeneration, which promote endothelial proliferation and arterial regeneration.
Keyphrases
- endothelial cells
- stem cells
- high glucose
- mouse model
- dendritic cells
- peripheral blood
- signaling pathway
- vascular endothelial growth factor
- wound healing
- blood flow
- nitric oxide
- immune response
- multiple sclerosis
- oxidative stress
- mesenchymal stem cells
- single cell
- intensive care unit
- hepatitis b virus
- respiratory failure
- wild type