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: 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)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Actins
• STAT3 Transcription Factor
• STAT5 Transcription Factor
• Angiotensin II
• Janus Kinase 2

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)