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.
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Authors | Annet Kirabo, S Paul Oh, Hideko Kasahara, Kay-Uwe Wagner, Peter P Sayeski |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 50
Issue 6
Pg. 1026-34
(Jun 2011)
ISSN: 1095-8584 [Electronic] England |
PMID | 21420414
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
Chemical References |
- Actins
- STAT3 Transcription Factor
- STAT5 Transcription Factor
- Angiotensin II
- Janus Kinase 2
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Topics |
- Actins
(metabolism)
- Angiotensin II
(pharmacology, therapeutic use)
- Animals
- Apoptosis
(drug effects, genetics)
- Cell Movement
(drug effects, genetics)
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects, genetics)
- Disease Models, Animal
- Female
- Fibrosis
(drug therapy, genetics)
- Janus Kinase 2
(genetics)
- Male
- Mice
- Mice, Knockout
- Muscle, Smooth, Vascular
(drug effects, metabolism)
- Neointima
(chemically induced, drug therapy, pathology)
- Phosphorylation
(drug effects, genetics)
- STAT3 Transcription Factor
(metabolism)
- STAT5 Transcription Factor
(metabolism)
- Signal Transduction
(drug effects, genetics)
- Vascular System Injuries
(drug therapy, pathology)
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