Published in:
Open Access
01-12-2015 | Research
Administered circulating microparticles derived from lung cancer patients markedly improved angiogenesis, blood flow and ischemic recovery in rat critical limb ischemia
Authors:
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
Published in:
Journal of Translational Medicine
|
Issue 1/2015
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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.