title: Platelet factor 4 mediates vascular smooth muscle cell injury responses.
abstract: Activated platelets release many inflammatory molecules with important roles in accelerating vascular inflammation. Much is known about platelet and platelet-derived mediator interactions with endothelial cells and leukocytes, but few studies have examined the effects of platelets on components of the vascular wall. Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to injury including the production of inflammatory molecules, cell proliferation, cell migration, and a decline in the expression of differentiation markers. In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model. PF4 drives a VSMC inflammatory phenotype including a decline in differentiation markers, increased cytokine production, and cell proliferation. We also demonstrate that PF4 effects are mediated, in part, through increased expression of the transcription factor Krüppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Guanfang
authors.initials: G
authors.lastname: Shi
authors.forename: David J
authors.initials: DJ
authors.lastname: Field
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Long
authors.forename: Deanne
authors.initials: D
authors.lastname: Mickelsen
authors.forename: Kyung-ae
authors.initials: KA
authors.lastname: Ko
authors.forename: Sara
authors.initials: S
authors.lastname: Ture
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Korshunov
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Miano
authors.forename: Craig N
authors.initials: CN
authors.lastname: Morrell
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D002339:Carotid Arteries / Q000166:cytology / Q000276:immunology; D020212:Carotid Artery Injuries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology* / Q000293:injuries*; D010978:Platelet Factor 4 / Q000378:metabolism*; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D010978:Platelet Factor 4