scholarly journals Nanoparticle-mediated endothelial cell-selective delivery of pitavastatin induces functional collateral arteries (therapeutic arteriogenesis) in a rabbit model of chronic hind limb ischemia

2010 ◽  
Vol 52 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Shinichiro Oda ◽  
Ryoji Nagahama ◽  
Kaku Nakano ◽  
Tetsuya Matoba ◽  
Mitsuki Kubo ◽  
...  
Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sebastian Cremer ◽  
Anne Klotzsche-von Ameln ◽  
Alessia Orlandi ◽  
Irina Korovina ◽  
Bettina Gercken ◽  
...  

Developmental endothelial locus-1 (Del-1) is an endothelial cell-derived secreted protein circulating in blood and associated with the cell surface and the extracellular matrix. As we previously demonstrated, Del-1 restricts leukocyte recruitment by inhibiting the β2-integrin, LFA-1. Leukocytes and progenitor cells (PC) may contribute to angiogenesis. The role of endogenous Del-1 in angiogenesis is elusive. We found, that physiological angiogenesis of the developing retina was not affected in the Del-1-/- mice compared to the wildtype (WT) mice. Surprisingly, Del-1-/- mice displayed a significantly increased angiogenic response compared to WT mice after induction of hind limb ischemia (144 ± 6 % increase of capillary density) and retinal ischemia (retinopathy of prematurity model) suggesting that endogenous Del-1 is an inhibitor of ischemia-induced neovascularization. Silencing of Del-1 with siRNA did not affect the angiogenic sprouting of endothelial cell (EC) spheroids, indicating that Del-1 blocks angiogenesis in a non-endothelial cell autonomous pathway. Soluble Del-1 blocked the adhesion of inflammatory cells on EC monolayers. In line with these results, ischemic muscles and ischemic retinae from Del-1-/- mice displayed an enhanced infiltration with inflammatory cells compared to the WT mice. Since Del-1 blocks inflammatory cell homing by inhibiting the leukocytic LFA-1-integrin, we addressed the role of the Del-1/LFA-1-integrin interaction on the inhibitory function of endogenous Del-1 on angiogenesis. Indeed, Del-1/LFA-1-double deficiency reversed the pro-angiogenic phenotype of the Del-1-/- mice to the level of WT mice in the model of hind limb ischemia. Thus, the inhibitory role of Del-1 on neovascularization is mediated by the interaction of Del-1 with the LFA-1-integrin. Moreover, Del-1-deficiency led to an increased homing of intravenously injected murine fluorescence-labeled WT Lin- BM PC in ischemic muscles in comparison to WT mice after the induction of hind limb ischemia. Taken together, Del-1 acts as a negative regulator of ischemia-induced angiogenesis by interacting with the LFA-1-integrin expressed in hematopoietic cells, thereby inhibiting the homing of hematopoietic cells to ischemic tissues.


2007 ◽  
Vol 22 (2) ◽  
pp. 104-108 ◽  
Author(s):  
Kazuhiko Doi ◽  
Tadashi Ikeda ◽  
Akira Marui ◽  
Toshihiro Kushibiki ◽  
Yoshio Arai ◽  
...  

2009 ◽  
Vol 49 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Masatake Katsu ◽  
Hiroyuki Koyama ◽  
Hiromitsu Maekawa ◽  
Hiroki Kurihara ◽  
Hiroaki Uchida ◽  
...  

Circulation ◽  
2004 ◽  
Vol 109 (4) ◽  
pp. 526-531 ◽  
Author(s):  
Noriyuki Tokunaga ◽  
Noritoshi Nagaya ◽  
Mikiyasu Shirai ◽  
Etsuro Tanaka ◽  
Hatsue Ishibashi-Ueda ◽  
...  

2003 ◽  
Vol 197 (4) ◽  
pp. 591-595 ◽  
Author(s):  
Jeffrey S Wilson ◽  
Greg Rushing ◽  
Brad L Johnson ◽  
Jeffrey A Kline ◽  
Jaime L Parker ◽  
...  

Radiology ◽  
2007 ◽  
Vol 245 (3) ◽  
pp. 761-769 ◽  
Author(s):  
Grigorios Korosoglou ◽  
Wesley D. Gilson ◽  
Michael Schär ◽  
Ali Ustun ◽  
Lawrence V. Hofmann ◽  
...  

2009 ◽  
Vol 192 (6) ◽  
pp. W306-W310 ◽  
Author(s):  
Ayumi Seko ◽  
Norihisa Nitta ◽  
Akinaga Sonoda ◽  
Shinichi Ohta ◽  
Masashi Takahashi ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. e16159 ◽  
Author(s):  
Karolien Jaspers ◽  
Bas Versluis ◽  
Tim Leiner ◽  
Petra Dijkstra ◽  
Marlies Oostendorp ◽  
...  

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