[Pitavastatin enhances angiogenesis and perfusion in a murine mode of limb ischemia].
OBJECTIVE
We investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia.


METHODS
C3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method.


RESULTS
Lower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group.


CONCLUSIONS
Pitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb ischemia.
Zhang
Yue-lan
YL
Department of Circulatory Medicine, First Affiliated Hospital, China Medical University, Shenyang 110001, China. zhyula@hotmail.com
Hu
Jian
J
Zhang
Zi-xin
ZX
Zeng
Ding-yin
DY
Qi
Guo-xian
GX
D000818:Animals; D004195:Disease Models, Animal; D007511:Ischemia / Q000503:physiopathology*; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000097:blood; D011804:Quinolines / Q000494:pharmacology*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D011804:Quinolines; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; C108475:pitavastatin