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Proangiogenic role of PPARá in the mouse hind limb ischemia model
Author(s) -
Rizvi Yasmeen,
Oyekan Adebayo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1148.19
Subject(s) - hindlimb , endocrinology , medicine , perfusion , vasoconstriction , ischemia , neovascularization , arteriogenesis , angiogenesis , ligation , chemistry , femoral artery , vasodilation
Angiogenesis (ANG) is a neovascularization response to tissue ischemia, tumor growth or inflammation. PPARá is a negative regulator of inflammation but its role in ANG is controversial. PPARá WT and KO mice were treated with vehicle or clofibrate (CF; 240 mg/kg) starting from 24h after ligation of the left femoral artery. Perfusion of both limbs was measured using laser Doppler flow meter or Imager system on days 0, 3, 7, 14, 21, 28, and 35. Vascular reactivity to AII (5–250 ng), PE (0.5– 2.5 ìg), SNP (0.5–2.5 ìg) and Ach (0.5–2.5 ìg) were determined in the Kreb's perfused hind limb preparation. Following ligation, perfusion was reduced (29±7%, WT; 25±4%; KO) followed by a time‐dependent recovery that was 72±23% (WT) and 37±9% (KO) on Day 35. Except for Day 3, CF did not affect perfusion in either group of mice suggesting a pro‐angiogenic role during early neovascularization. AII‐induced increase in perfusion pressure was two‐fold greater between Days 3 and 7/14 but markedly reduced at Day 35. By contrast, PE‐induced vasoconstriction was unchanged. CF inhibited AII responses on Days 7,14 and 35 but elicited no effect on Day 3 while it inhibited PE response on Days 3 and 35. CF enhanced SNP response on Day 35 whereas Ach response remained unchanged. These data demonstrate that PPARá promotes ANG in the mouse hind limb ischemia model. In addition, vascular reactivity appears to be independent of recovery in perfusion in this model.