title: Activation of transient receptor potential vanilloid 1 accelerates re-endothelialization and inhibits neointimal formation after vascular injury.
abstract: OBJECTIVE
  Transient receptor potential vanilloid 1 (TRPV1) is an important regulator of endothelial function, but the effects of TRPV1 on endothelial recovery and neointimal formation after vascular injury remain elusive. We tested the effects of activating TRPV1 using capsaicin on re-endothelialization and neointimal formation after wire-induced injury of the carotid artery in mice.
  
  
  METHODS
  The human umbilical vein endothelial cells (HUVECs) were treated with the TRPV1 agonist capsaicin, its antagonist capsazepine, intracellular calcium chelator BAPTA, or mitofusin 2 (Mfn2)-specific short interfering RNA (siRNA). The migration, proliferation, mitochondrial morphology, membrane potential, and adenosine triphosphate production were measured. The carotid artery wire injury procedure was performed in male TRPV1 knockout mice and C57BL/6J wild-type (WT) mice that were then treated with or without Mfn2 siRNA. The re-endothelialization and neointimal formation were evaluated.
  
  
  RESULTS
  Capsaicin significantly enhanced the migration and proliferation of HUVECs. Both capsazepine and BAPTA abolished capsaicin-induced migration and proliferation of HUVECs. In addition, capsaicin stimulated the formation of reticular mitochondria, augmented mitochondrial membrane potential, increased adenosine triphosphate production, and upregulated Mfn2. However, these effects were attenuated by knockdown of Mfn2 with specific siRNA. Dietary capsaicin markedly accelerated re-endothelialization and inhibited neointimal formation in WT mice but not in TRPV1 knockout mice. Moreover, Mfn2 siRNA also attenuated capsaicin-induced enhancement of endothelial recovery and suppression of neointimal hyperplasia in WT mice.
  
  
  CONCLUSIONS
  Activation of TRPV1 with capsaicin attenuates neointimal formation by accelerating re-endothelialization through upregulation of Mfn2.
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Linan
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Yunrong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Kecheng
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Pei
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China. Electronic address: yangdc71@126.com.
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D065096:Calcium Chelating Agents / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006965:Hyperplasia; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D058426:Neointima; D034622:RNA Interference; D062326:Re-Epithelialization / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D065096:Calcium Chelating Agents; D024101:Mitochondrial Proteins; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C488751:Mfn2 protein, mouse; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C071423:capsazepine; D002211:Capsaicin