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Role of ROS in ischemia‐induced lung angiogenesis
Author(s) -
Nijmeh Julie,
Biswal Shyam,
Wagner Elizabeth
Publication year - 2007
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.21.6.a1217-a
Subject(s) - angiogenesis , lung , reactive oxygen species , ischemia , intraperitoneal injection , acetylcysteine , pharmacology , medicine , downregulation and upregulation , ligation , chemistry , endocrinology , immunology , antioxidant , biochemistry , gene
Reactive oxygen species (ROS) have been shown to play a role in promoting angiogenesis. We have developed a mouse model where left pulmonary artery ligation (LPAL) consistently induces the formation of a new systemic vasculature to the ischemic lung. To investigate whether ROS play a role in angiogenesis in our model, we assessed the effects of ROS down‐regulation by pre‐treating mice with N‐acetylcysteine (NAC) (n=7). We also assessed the effects of ROS upregulation using mice deficient in the antioxidant promoting transcription factor Nrf2 (n=8) on new vessel growth. Pretreatment of C57Bl/6J mice with intraperitoneal NAC (5mg/10g body weight) at 24, 12 and 0 hours prior to LPAL and orally for 14 days afterwards resulted in a decrease in systemic blood flow to the left lung as assessed by radiolabeled microspheres compared to vehicle treated controls (54% control; p<0.002). Furthermore, Nrf2‐deficient mice (CD‐1) 14 days after LPAL demonstrated a significant increase in blood flow relative to wild type CD‐1 LPAL mice (200% control; p<0.02). These data collectively suggest that ROS are involved in promoting systemic angiogenesis in response to chronic non‐hypoxic ischemia in the mouse lung. NHLBI, HL71605