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

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish
Pages (from-to)796-801
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number6
DOIs
Publication statusPublished - Jun 1 2009

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Nanotechnology
Vascular Endothelium
Nanoparticles
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide Synthase Type III
Angiogenesis Inducing Agents
Intercellular Signaling Peptides and Proteins
Ischemia
Therapeutics
Intramuscular Injections
Therapeutic Uses
Hindlimb
Nitric Oxide Synthase
Protein Kinases
Extremities
Perfusion
pitavastatin
Muscles

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium. / Kubo, Mitsuki; Egashira, Kensuke; Inoue, Takahiro; Koga, Jun Ichiro; Oda, Shinichiro; Chen, Ling; Nakano, Kaku; Matoba, Tetsuya; Kawashima, Yoshiaki; Hara, Kaori; Tsujimoto, Hiroyuki; Sueishi, Katsuo; Tominaga, Ryuji; Sunagawa, Kenji.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 29, No. 6, 01.06.2009, p. 796-801.

Research output: Contribution to journalArticle

Kubo, M, Egashira, K, Inoue, T, Koga, JI, Oda, S, Chen, L, Nakano, K, Matoba, T, Kawashima, Y, Hara, K, Tsujimoto, H, Sueishi, K, Tominaga, R & Sunagawa, K 2009, 'Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium', Arteriosclerosis, thrombosis, and vascular biology, vol. 29, no. 6, pp. 796-801. https://doi.org/10.1161/ATVBAHA.108.182584
Kubo, Mitsuki ; Egashira, Kensuke ; Inoue, Takahiro ; Koga, Jun Ichiro ; Oda, Shinichiro ; Chen, Ling ; Nakano, Kaku ; Matoba, Tetsuya ; Kawashima, Yoshiaki ; Hara, Kaori ; Tsujimoto, Hiroyuki ; Sueishi, Katsuo ; Tominaga, Ryuji ; Sunagawa, Kenji. / Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium. In: Arteriosclerosis, thrombosis, and vascular biology. 2009 ; Vol. 29, No. 6. pp. 796-801.
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