title: Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is a common disease accounting for about 12% of the adult population, and causes significant morbidity and mortality. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients. In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD.
  
  
  RESULTS
  We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 (AGGF1 group) resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice with injection of the empty vector (control group). Color PW Doppler echocardiography showed that the blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration (n = 9/group, P = 0.049, 0.001, and 0.001, respectively). Increased blood flow in the AGGF1 group was correlated to increased density of CD31-positive vessels and decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. Ambulatory impairment was significantly reduced in the AGGF1 group compared to the control group (P = 0.004). The effect of AGGF1 was dose-dependent. At day 28 after gene transfer, AGGF1 was significantly better in increasing blood flow than FGF-2 (P = 0.034), although no difference was found for tissue necrosis and ambulatory impairment.
  
  
  CONCLUSIONS
  These data establish AGGF1 as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Qiulun
authors.initials: Q
authors.lastname: Lu
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yao
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yao
authors.forename: Shizhi
authors.initials: S
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.forename: Bisheng
authors.initials: B
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.forename: Gangjian
authors.initials: G
authors.lastname: Qin
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.forename: Chengqi
authors.initials: C
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006614:Hindlimb / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D058729:Peripheral Arterial Disease / Q000378:metabolism / Q000628:therapy
chemical_list: C482200:AGGF1 protein, human; D042501:Angiogenic Proteins