title: Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium.
abstract: OBJECTIVE
  Recent clinical studies of therapeutic neovascularization using angiogenic growth factors demonstrated smaller therapeutic effects than those reported in animal experiments. We hypothesized that nanoparticle (NP)-mediated cell-selective delivery of statins to vascular endothelium would more effectively and integratively induce therapeutic neovascularization.
  
  
  RESULTS
  In a murine hindlimb ischemia model, intramuscular injection of biodegradable polymeric NP resulted in cell-selective delivery of NP into the capillary and arteriolar endothelium of ischemic muscles for up to 2 weeks postinjection. NP-mediated statin delivery significantly enhanced recovery of blood perfusion to the ischemic limb, increased angiogenesis and arteriogenesis, and promoted expression of the protein kinase Akt, endothelial nitric oxide synthase (eNOS), and angiogenic growth factors. These effects were blocked in mice administered a nitric oxide synthase inhibitor, or in eNOS-deficient mice.
  
  
  CONCLUSIONS
  NP-mediated cell-selective statin delivery may be a more effective and integrative strategy for therapeutic neovascularization in patients with severe organ ischemia.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Mitsuki
authors.initials: M
authors.lastname: Kubo
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Koga
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Oda
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Kaku
authors.initials: K
authors.lastname: Nakano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matoba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Kaori
authors.initials: K
authors.lastname: Hara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tominaga
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa