title: Curcumin accelerates reendothelialization and ameliorates intimal hyperplasia in balloon-injured rat carotid artery via the upregulation of endothelial cell autophagy.
abstract: Delayed reendothelialization and intimal hyper-plasia (IH) contribute to the failure of vascular interventions. Curcumin (Cur) has been used for various types of diseases with antioxidant, antiproliferative and anti‑inflammatory effects. However, investigations involving the application of Cur in inhibiting IH are limited. The aim of the present study was to evaluate the potential therapeutic effects of Cur and its underlying mechanisms on a rat model of carotid artery (CA) intimal injury. In vitro, an endothelial cell (EC) migration assay was conducted using cultured primary human umbilical vein endothelial cells (HUVECs) that were exposed to Cur. In vivo, CA angioplasty injury was used to generate a rat model of intimal injury. CAs were collected at 3 days, and 1 and 4 weeks after injury, respectively, for western blot analysis and double-immunofluorescence analyses, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, oxidative stress indicator analysis and hematoxylin and eosin staining of the neointima. In vivo, Cur significantly enhanced the migration and healing of HUVECs and simultaneously promoted microtubule-associated protein light chain 3-II (LC3-II) expression when HUVECs were subjected to an artificial scratch. In vitro, endangium from the Cur-treated rats exhibited a significantly reduced number of apoptotic ECs and oxidative stress level compared to that of the sham group. In addition, Cur treatment markedly improved quantification of the LC3-II concomitant with the downregulation of p62 in the injured CA. At 1 week following injury, sizable neointimal lesions had developed, although prominent intima thickening was not observed. At 4 weeks, apparent hemadostenosis occurred resulting from the exorbitance IH. Cur treatment markedly reduced the thickness of the neointimal lesion. It is noteworthy that high-dose Cur may have exerted more significant effects than low-dose Cur. Cur can potentially become a therapeutic drug for angiostenosis by imparting a protective effect that accelerates reendothelialization and ameliorates IH and was mediated by its pro-autophagic effect.
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Fengxuan
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Guilin
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000071456:Sequestosome-1 Protein; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D000071456:Sequestosome-1 Protein; C526109:Anxa3 protein, rat; C491079:Sqstm1 protein, rat