Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice

Document Type

Article

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 (AT1-R) resulting in enhanced cell growth. However, the role that Jak2 plays in AT1-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. © 2011 Elsevier Ltd.

Keywords

Angiotensin II, Jak2, Neointima, Vascular injury, Vascular smooth muscle cells

Publication Date

6-1-2011

Publication Title

Journal of Molecular and Cellular Cardiology

ISSN

00222828

Volume

50

Issue

6

First Page

1026

Last Page

1034

PubMed ID

21420414

Digital Object Identifier (DOI)

10.1016/j.yjmcc.2011.03.005

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