title: The transcription factor ETS-1 mediates proinflammatory responses and neointima formation in carotid artery endoluminal vascular injury.
abstract: The transcription factor ETS-1 is a critical mediator of vascular inflammation and hypertrophy in hypertension. We tested the hypothesis that ETS-1 is a mediator of proinflammatory responses and neointimal hyperplasia after balloon injury of the carotid artery. For this study, we took advantage of the availability of an ETS-1 dominant-negative (DN) peptide. Sprague-Dawley rats were assigned to treatment with ETS-1 DN, a mutant peptide (ETS-1 MU), or vehicle (Veh) and subjected to balloon injury of the carotid artery. After 2, 24 hours, and 14 days, the rats were euthanized, and both carotid arteries were processed for real-time polymerase chain reaction (2 hours), immunofluorescence and immunohistochemistry (24 hours), and morphometric analysis (14 days). ETS-1 mRNA was up regulated (2.4-fold) in injured carotid arteries. By immunofluorescence, we confirmed increased nuclear expression of ETS-1 24 hours postinjury. The carotid artery mRNA expression of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-2, P-selectin, E-selectin, vascular cell adhesion molecule, and intercellular adhesion molecule was increased 2 hours after injury. ETS-1 DN but not ETS-1 MU significantly reduced mRNA and protein expression for monocyte chemotactic protein-1, P-selectin, and E-selectin in injured arteries. These changes were accompanied by concomitant reductions in vascular monocyte and leukocyte infiltration. Moreover, treatment with ETS-1 DN but not ETS-1 MU resulted in a 50% reduction in neointima formation at day 14 after balloon injury. This study unveils the role of ETS-1 as a mediator of inflammation and neointima formation in a model of carotid artery balloon injury and may result in the development of novel strategies in the treatment of vascular injury.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Feng
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.forename: Ping
authors.initials: P
authors.lastname: Hua
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Jaimes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002404:Catheterization; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D011336:Probability; D050784:Proto-Oncogene Protein c-ets-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D016207:Cytokines; D019040:E-Selectin; D019007:P-Selectin; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D014157:Transcription Factors