title: Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice.
abstract: The in vitro treatment of vascular smooth muscle cells (VSMC) with angiotensin II (Ang II) causes Janus kinase 2 (Jak2) to interact with the Ang II type 1 receptor (AT(1)-R) resulting in enhanced cell growth. However, the role that Jak2 plays in AT(1)-R-mediated vascular cell growth and remodeling in vivo is less clear. We hypothesized that in vivo, Jak2 plays a rate-limiting role in Ang II-mediated neointima formation following vascular injury. Using the Cre-loxP system, we conditionally ablated Jak2 from the VSMC of mice. We found that these mice are protected from Ang II-mediated neointima formation following iron chloride-induced vascular injury. In addition, the VSMC Jak2 null mice were protected from injury-induced vascular fibrosis and the pathological loss of the contractile marker, smooth muscle α-actin. Finally, when compared to controls, the VSMC Jak2 null mice exhibited significantly less Ang II-induced VSMC proliferation and migration in vitro and in vivo and more apoptosis. These results suggest that Jak2 plays a central role in the causation of Ang II-induced neointima formation following vascular injury and may provide a novel target for the prevention of neointima formation.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Annet
authors.initials: A
authors.lastname: Kirabo
authors.forename: S Paul
authors.initials: SP
authors.lastname: Oh
authors.forename: Hideko
authors.initials: H
authors.lastname: Kasahara
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
authors.forename: Peter P
authors.initials: PP
authors.lastname: Sayeski
mesh_terms: D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D058426:Neointima / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D057772:Vascular System Injuries / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000199:Actins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D000804:Angiotensin II; D053614:Janus Kinase 2