PMID- 20206620
OWN - NLM
STAT- MEDLINE
DCOM- 20101101
LR  - 20220321
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 634
IP  - 1-3
DP  - 2010 May 25
TI  - 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.
PG  - 121-31
LID - 10.1016/j.ejphar.2010.02.038 [doi]
AB  - 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, Nomega-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.
CI  - Copyright 2010 Elsevier B.V. All rights reserved.
FAU - Qi, Xun
AU  - Qi X
AD  - Department of Physiology, Kanazawa University Graduate School of Medicine, 13-1 
      Takara-machi, Kanazawa, Ishikawa 920-8640, Japan.
FAU - Okamoto, Yasuo
AU  - Okamoto Y
FAU - Murakawa, Tomomi
AU  - Murakawa T
FAU - Wang, Fei
AU  - Wang F
FAU - Oyama, Osamu
AU  - Oyama O
FAU - Ohkawa, Ryunosuke
AU  - Ohkawa R
FAU - Yoshioka, Kazuaki
AU  - Yoshioka K
FAU - Du, Wa
AU  - Du W
FAU - Sugimoto, Naotoshi
AU  - Sugimoto N
FAU - Yatomi, Yutaka
AU  - Yatomi Y
FAU - Takuwa, Noriko
AU  - Takuwa N
FAU - Takuwa, Yoh
AU  - Takuwa Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100303
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Lysophospholipids)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Delayed-Action Preparations/administration & dosage
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/*physiology
MH  - Hindlimb/blood supply/drug effects
MH  - Ischemia/*drug therapy/enzymology/*physiopathology
MH  - Lactic Acid/*administration & dosage
MH  - Lysophospholipids/*administration & dosage
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microspheres
MH  - Neovascularization, Pathologic/drug therapy/enzymology/physiopathology
MH  - Neovascularization, Physiologic/*drug effects/physiology
MH  - Nitric Oxide Synthase Type III/*physiology
MH  - Polyglycolic Acid/*administration & dosage
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Random Allocation
MH  - Regional Blood Flow/drug effects/physiology
MH  - Sphingosine/administration & dosage/*analogs & derivatives
EDAT- 2010/03/09 06:00
MHDA- 2010/11/03 06:00
CRDT- 2010/03/09 06:00
PHST- 2009/11/02 00:00 [received]
PHST- 2010/01/25 00:00 [revised]
PHST- 2010/02/14 00:00 [accepted]
PHST- 2010/03/09 06:00 [entrez]
PHST- 2010/03/09 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
AID - S0014-2999(10)00161-5 [pii]
AID - 10.1016/j.ejphar.2010.02.038 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 May 25;634(1-3):121-31. doi: 10.1016/j.ejphar.2010.02.038. 
      Epub 2010 Mar 3.