Deletion of Vascular Smooth Muscle Jak2 Prevents Angiotensin II‐induced Neointima Formation Following Vascular Injury in Mice

The in vitro treatment of vascular smooth muscle cells (VSMC) with angiotensin II (Ang II) causes Janus kinase 2 (Jak2) to physically interact with the Ang II type 1 receptor (AT1–R) and this correlates with 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. To test this, we utilized the Cre‐loxP system to conditionally ablate Jak2 from the VSMC of mice. We found that these mice were protected from Ang II‐mediated neointima formation following iron chloride‐induced vascular injury. The VSMC Jak2 null mice had a lower media/intima ratio (0.19 ± 0.04 vs. 1.28 ± 0 .27) and had reduced narrowing of the carotid artery lumen when compared to controls. In addition, the VSMC Jak2 null mice were protected from injury induced vascular fibrosis and the pathological loss of the contractile marker, smooth muscle á‐actin. Finally, the VSMC Jak2 null mice exhibited significantly less Ang II induced VSMC proliferation and migration in vitro and in vivo. Collectively, these results suggest that in vivo, Jak2 plays a central role in the causation of Ang II‐induced neointima formation following vascular injury. Support: NIH Award R01‐HL67277, AHA GIA Award #0855361E and AHA Pre‐Doctoral Fellowship #10PRE4310065.