title: IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation.
abstract: The role of inflammation on atherosclerosis and restenosis is well established. Restenosis is thought to be a complex response to injury, which includes early thrombus formation, acute inflammation and neo-intimal growth. Inflammatory cells are likely contributors in the host response to vascular injury, via cytokines and chemokines secretion, including TNF-alpha (TNF). We have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (ECs) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL-10KO) displayed significantly delayed Re-endothelialization and enhanced neo-intimal growth compared to their WT counterparts. Exogenous recombinant IL-10 treatment dramatically blunted the neo-intimal thickening while significantly accelerating the recovery of the injured endothelium in WT mice. In vitro, IL-10 inhibited negative effects of TNF on ECs proliferation, ECs cell cycle, ECs-monocyte adhesion and ECs apoptosis. Furthermore, IL-10 treatment attenuated TNF-induced smooth muscle cells proliferation. Our data suggest that IL-10 differentially regulate endothelial and vascular smooth cells proliferation and function and thus inhibits neo-intimal hyperplasia. Thus, these results may provide insights necessary to develop new therapeutic strategies to limit vascular restenosis during percutaneous coronary intervention (PCI) in the clinics.
authors.affiliation: Center for Translational Medicine, Temple University, Philadelphia, Pennsylvania United States of America.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Verma
authors.affiliation: Center for Translational Medicine, Temple University, Philadelphia, Pennsylvania United States of America.
authors.forename: Venkata Naga Srikanth
authors.initials: VN
authors.lastname: Garikipati
authors.affiliation: Department of Cardiovascular Science, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Center for Translational Medicine, Temple University, Philadelphia, Pennsylvania United States of America.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Khan
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Tina
authors.initials: T
authors.lastname: Thorne
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Qin
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.affiliation: Center for Translational Medicine, Temple University, Philadelphia, Pennsylvania United States of America.|Department of Pharmacology, Temple University, Philadelphia, Pennsylvania United States of America.
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D059447:Cell Cycle Checkpoints / Q000502:physiology; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000473:pathology*; D006965:Hyperplasia; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10