title: (2-Hydroxypropyl)-β-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis.
abstract: BACKGROUND
  Peripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that β-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-β-cyclodextrin (2HP-β-CD).
  
  
  RESULTS
  2HP-β-CD significantly increased vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor BB (PDGF-BB) peptides in human umbilical vein endothelial cells (HUVECs) and also increased basic fibroblast growth factor (bFGF) peptide in human aortic smooth muscle cells (HASMCs). 2HP-β-CD stimulated both proliferation and migration of HUVECs in an endothelial nitric oxide synthase (eNOS)/NO-dependent manner, whereas NO was found to be involved in proliferation, but not migration, of HASMCs. In a unilateral hindlimb ischemia model in mice, 2HP-β-CD injections not only promoted blood flow recovery and increased microvessel densities in ischemic muscle, but also promoted coverage of the vessels with smooth muscle cells, thus stabilizing the vessels. Administration of 2HP-β-CD increased the expression of several angiogenic factors, including VEGF-A, PDGF-BB and transforming growth factor beta-1 (TGF-β1) in ischemic muscle. Injections of 2HP-β-CD also stimulated protein kinase B and extracellular regulated protein kinases (ERK), leading to an increase in phosphorylation of eNOS in ischemic muscle. Treatment with the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), showed that stimulation of blood flow induced by 2HP-β-CD was partially dependent on NO.
  
  
  CONCLUSIONS
  Therapeutic angiogenesis by 2HP-β-CD may be beneficial to patients with PAD.
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qi
authors.affiliation: Hospital infection management office, Liaoning Cancer Hospital & Institute, Shenyang, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhai
authors.affiliation: Department of neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Gefei
authors.initials: G
authors.lastname: Guan
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Yu
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D012039:Regional Blood Flow / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III