title: Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis.
abstract: Multiple factors regulate arteriogenesis. Peripheral nerves play a crucial role in vascular remodeling, but the function of peripheral nerves during arteriogenesis is obscure. Our study investigated the contribution of denervation to arteriogenesis during post-ischemic recovery from hindlimb femoral artery ligation.
  
  
  
  Sprague-Dawley rats were randomly allocated into four groups of normal control (NC), hindlimb ischemia (HI), hindlimb ischemia with denervation (HID) and hindlimb simple denervation (HD). Hindlimb ischemic recovery was assessed by clinical assessment and tibialis anterior muscle remodeling on day 28 post-surgery. Blood flow was determined by laser Doppler imaging on day 0, 3, 7, 14 and 28 post-surgery. Collateral number of hindlimb was observed by angiography and gracilis muscles were tested by immunostaining on day 7 and 28 post-surgery. Angiogenesis was accessed by counting CD31 positive capillaries in tibialis anterior muscles on day 28 post-surgery. Group HID showed impaired ischemic recovery compared with the other 3 groups and impaired blood flow recovery compared with group HI on day 28 post-surgery. The collateral number and capillary density of group HID were lower than group HI. The collateral diameter of both group HID and group HI significantly increased compared with group NC. However, the lumen diameter was much narrower and the vessel wall was much thicker in group HID than group HI. We also demonstrated that the thickened neointima of collaterals in group HID comprised of smooth muscle cells and endothelial cells.
  
  
  
  Denervation of the ligated femoral artery in the hindlimb impairs ischemic recovery via impaired perfusion. The possible mechanisms of impaired perfusion are lower collateral number, lower capillary density and most likely narrower lumen, which damage ischemic recovery. This study illustrates the crucial role of peripheral nerves in arteriogenesis using a model combined ischemia with denervation in hindlimb.
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yinghuan
authors.initials: Y
authors.lastname: Cen
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuansen
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Laboratory of Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Huijin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology; D049109:Cell Proliferation; D003097:Collateral Circulation; D003714:Denervation; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000294:innervation* / Q000601:surgery*; D005455:Fluorescent Antibody Technique; D006614:Hindlimb / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D008026:Ligation; D009132:Muscles / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D018919:Neovascularization, Physiologic; D010477:Perfusion; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1