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

Annet Kirabo, S. Paul Oh, Hideko Kasahara, Kay Uwe Wagner, Peter P. Sayeski

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1026-1034
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume50
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Janus Kinase 2
Neointima
Vascular Smooth Muscle
Angiotensin II
Vascular System Injuries
Smooth Muscle Myocytes
Wounds and Injuries
Angiotensin Type 1 Receptor
Growth
Causality
Cell Movement
Smooth Muscle
Blood Vessels
Actins
Chlorides
Fibrosis
Iron
Cell Proliferation
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice. / Kirabo, Annet; Oh, S. Paul; Kasahara, Hideko; Wagner, Kay Uwe; Sayeski, Peter P.

In: Journal of Molecular and Cellular Cardiology, Vol. 50, No. 6, 01.06.2011, p. 1026-1034.

Research output: Contribution to journalArticle

Kirabo, Annet ; Oh, S. Paul ; Kasahara, Hideko ; Wagner, Kay Uwe ; Sayeski, Peter P. / Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice. In: Journal of Molecular and Cellular Cardiology. 2011 ; Vol. 50, No. 6. pp. 1026-1034.
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