Liposomal Hsp90 cDNA induces neovascularization via nitric oxide in chronic ischemia

Objective: Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation, the latter involving Hsp90 as a chaperone protein. Here, we investigated the potential of regional Hsp90 overexpression to induce therapeutic neovascularization in vivo in a chronic rabbit hindlimb ischemia model. Methods: In rabbits (n=7 per group), the external femoral artery was excised at day 0 (0). At d7, liposomes containing eGFP (control group) or Hsp90 were retroinfused into the anterior tibial vein. At day 7 and day 35, angiographies were obtained and analyzed for collateral formation and perfusion velocity (frame count score) (% of d7 values). Capillary/muscle fiber (C/MF) ratio was calculated from five muscle areas of the ischemic limb. L-NAME and Geldanamycin were co-applied, where indicated. Results: Compared to mock-treated controls, Hsp90 transfected increased C/MF ratio at day 35 (1.78 +/- 0.15 vs. 1.19 +/- 0.13, p