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Sustained delivery of sphingosine-1-phosphate using poly(lactic-co-glycolic acid)-based microparticles stimulates Akt/ERK-eNOS mediated angiogenesis and vascular maturation restoring blood flow in ischemic limbs of mice
- フォーマット:
- 論文
- 責任表示:
- Qia, Xun ; Okamoto, Yasuo ; Murakawa, Tomomi ; Wang, Fei ; Oyama, Osamu ; Ohkawa, Ryunosuke ; Yoshioka, Kazuaki ; Du, Wa ; Sugimoto, Naotoshi ; Yatomi, Yutaka ; Takuwa, Noriko ; Takuwa, Yoh
- 言語:
- 英語
- 出版情報:
- Elsevier BV, 2010-05-01
- 著者名:
Qia, Xun Okamoto, Yasuo Murakawa, Tomomi Wang, Fei Oyama, Osamu Ohkawa, Ryunosuke Yoshioka, Kazuaki Du, Wa Sugimoto, Naotoshi Yatomi, Yutaka Takuwa, Noriko Takuwa, Yoh - 掲載情報:
- European Journal of Pharmacology
- ISSN:
- 0014-2999
- 巻:
- 634
- 通号:
- 1-3
- 開始ページ:
- 121
- 終了ページ:
- 131
- バージョン:
- author
- 概要:
- 金沢大学医薬保健研究域医学系<br />Therapeutic angiogenesis is a promising strategy for treating ischemia. The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration and tube formation, and … plays the critical role in developmental angiogenesis. We developed poly(lactic-co-glycolic-acid) (PLGA)-based S1P-containing microparticles (PLGA-S1P), which are biodegradable and continuously release S1P, and studied the effects of PLGA-S1P on neovascularization in murine ischemic hindlimbs. Intramuscular injections of PLGA-S1P stimulated blood flow in C57BL/6 mice dose-dependently, with repeated administrations at a 3-day interval, rather than a single bolus or 6-day interval, over 28. days conferring the optimal stimulating effect. In Balb/c mice that exhibit limb necrosis and dysfunction due to retarded blood flow recovery, injections of PLGA-S1P stimulated blood flow with alleviation of limb necrosis and dysfunction. PLGA-S1P alone did not induce edema in ischemic limbs, and rather blocked vascular endothelial growth factor-induced edema. PLGA-S1P not only increased the microvessel densities in ischemic muscle, but promoted coverage of vessels with smooth muscle cells and pericytes, thus stabilizing vessels. PLGA-S1P stimulated Akt and ERK with increased phosphorylation of endothelial nitric oxide synthase in ischemic muscle. The effects of the nitric oxide synthase inhibitor, Nω-nitro-l-arginine methylester, showed that PLGA-S1P-induced blood flow stimulation was partially dependent on nitric oxide. Injections of PLGA-S1P also increased the expression of angiogenic factors and the recruitment of CD45-, CD11b- and Gr-1-positive myeloid cells, which are implicated in post-ischemic angiogenesis, into ischemic muscle. These results indicate that PLGA-based, sustained local delivery of S1P is a potentially useful therapeutic modality for stimulating post-ischemic angiogenesis. © 2010 Elsevier B.V. 続きを見る
- URL:
- http://hdl.handle.net/2297/23922
類似資料:
American Society for Clinical Investigation | |
International Union of Biochemistry and Molecular Biology, Inc / Wiley-Blackwell | |
American Association for Cancer Research | |
International Union of Biochemistry and Molecular Biology, Inc. / Wiley-Blackwell |
Oxford University Press (OUP) |