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

J Mol Cell Cardiol. 2011 Jun;50(6):1026-34. doi: 10.1016/j.yjmcc.2011.03.005. Epub 2011 Mar 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Angiotensin II / pharmacology*
  • Angiotensin II / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Disease Models, Animal
  • Female
  • Fibrosis / drug therapy
  • Fibrosis / genetics
  • Janus Kinase 2 / genetics*
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism*
  • Neointima* / chemically induced
  • Neointima* / drug therapy
  • Neointima* / pathology
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • STAT3 Transcription Factor / metabolism
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Vascular System Injuries / drug therapy*
  • Vascular System Injuries / pathology


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