Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium

Mitsuki Kubo, Kensuke Egashira, Takahiro Inoue, Jun Ichiro Koga, Shinichiro Oda, Ling Chen, Kaku Nakano, Tetsuya Matoba, Yoshiaki Kawashima, Kaori Hara, Hiroyuki Tsujimoto, Katsuo Sueishi, Ryuji Tominaga, Kenji Sunagawa

研究成果: ジャーナルへの寄稿学術誌査読

58 被引用数 (Scopus)

抄録

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. METHODS AND 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.

本文言語英語
ページ(範囲)796-801
ページ数6
ジャーナルArteriosclerosis, thrombosis, and vascular biology
29
6
DOI
出版ステータス出版済み - 6月 2009

!!!All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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