Administered circulating microparticles derived from lung cancer patients markedly improved angiogenesis, blood flow and ischemic recovery in rat critical limb ischemia

Jiunn Jye Sheu, Fan Yen Lee, Christopher Glenn Wallace, Tzu Hsien Tsai, Steve Leu, Yung Lung Chen, Han Tan Chai, Hung I. Lu, Cheuk Kwan Sun*, Hon Kan Yip

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

20 Scopus citations

Abstract

Background: We hypothesized that lung cancer patient's circulating microparticles (Lc-MPs) could promote angiogenesis, blood flow in ischemic zone and ischemic recovery in rat critical limb ischemia (CLI). Methods: To investigate the impact of MP therapy on reversing the setting of CLI, adult-male Sprague-Dawley rats (n=50) equally randomized into sham control (SC) (group 1), SC-Lc-MPs (1.0 x 107 particles) (group 2), CLI (group 3), CLI-Hs-MPs (MPs from healthy-subject) (group 4), and CLI-Lc-MPs (group 5) were sacrificed by post-CLI day-14. Results: In vitro study showed that Lc-MPs enhanced VEGFR2 expression, angiogenesis, nitric-oxide production, and endothelial cell proliferation (all p<0.005). By days 7 and 14, Laser Doppler showed significantly higher ischemic/normal blood-flow ratio in groups 1 and 2 compared with group 3, and was significantly higher in group 4 and further elevated in group 5 (p<0.0001). Numbers of small vessels and endothelial markers (CD31+ and vWF+ cells) and protein expressions (eNOS, CD31) exhibited a pattern identical to Lasre Doppler among the five groups (all p<0.001). Pro-angiogenic factors (VEGF, CXCR4, SDF-1α HGF) at cellular and protein levels showed a significant step-wise increase from groups 1 and 2 to groups 3, 4, and 5 (all p<0.001). Protein expressions of fibrotic (Smad3, TGF-β) and apoptotic (mitochondrial Bax, cleaved caspase 3, and PARP) biomarkers displayed an opposite pattern compared to that of Laser Doppler, whereas the protein expressions of anti-fibrotic (Smad1/5, BMP-2) and anti-apoptotic (Bcl-2) biomarkers showed an identical pattern compared with that of Laser Doppler among groups 1 to 3, and 5 (all p<0.001). Conclusion: Administration of Lc-MPs augmented angiogenesis and restored blood flow in a rat of CLI.

Original languageEnglish
Article number59
JournalJournal of Translational Medicine
Volume13
Issue number1
DOIs
StatePublished - 15 02 2015

Bibliographical note

Publisher Copyright:
© Sheu et al.; licensee BioMed Central.

Keywords

  • Angiogenesis
  • Blood-flow restoration
  • Circulating microparticles
  • Critical limb ischemia
  • Lung cancer

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