title: Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis.
abstract: OBJECTIVE
  Activation of transient receptor potential vanilloid type-1 (TRPV1) channels may affect lipid storage and the cellular inflammatory response. Now, we tested the hypothesis that activation of TRPV1 channels attenuates atherosclerosis in apolipoprotein E knockout mice (ApoE(-/-)) but not ApoE(-/-)TRPV1(-/-) double knockout mice on a high-fat diet.
  
  
  RESULTS
  Both TRPV1 mRNA and protein expression were identified in vascular smooth muscle cells (VSMC) and in aorta from C57BL/6J mice using RT-PCR, immunoblotting, and immunohistochemistry. In vitro, activation of TRPV1 by the specific agonists capsaicin and resiniferatoxin dose-dependently increased cytosolic calcium and significantly reduced the accumulation of lipids in VSMC from C57BL/6J mice but not from TRPV1(-/-) mice. TRPV1 activation increased ATP-binding cassette transporter A1 (ABCA1) expression and reduced low-density lipoprotein-related protein 1 (LRP1) expression in VSMC by calcium-dependent and calcineurin- and protein kinase A-dependent mechanisms. These results showed increased cellular cholesterol efflux and reduced cholesterol uptake. In vivo, long-term activation of TRPV1 by capsaicin for 24 weeks increased ABCA1 and reduced LRP1 expression in aorta from ApoE(-/-) mice on a high-fat diet. Long-term activation of TRPV1 significantly reduced lipid storage and atherosclerotic lesions in the aortic sinus and in the thoracoabdominal aorta from ApoE(-/-) mice but not from ApoE(-/-)TRPV1(-/-) mice on a high-fat diet. These findings indicated that TRPV1 activation ameliorates high-fat diet-induced atherosclerosis.
  
  
  CONCLUSIONS
  Activation of TRPV1 may be a novel therapeutic tool to attenuate atherosclerosis caused by a high-fat diet.
authors: Department of Hypertension and Endocrinology,  Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042,  People' s Republic of China.
authors: Liqun
authors: L
authors: Ma
authors: Jian
authors: J
authors: Zhong
authors: Zhigang
authors: Z
authors: Zhao
authors: Zhidan
authors: Z
authors: Luo
authors: Shuangtao
authors: S
authors: Ma
authors: Jing
authors: J
authors: Sun
authors: Hongbo
authors: H
authors: He
authors: Tianqi
authors: T
authors: Zhu
authors: Daoyan
authors: D
authors: Liu
authors: Zhiming
authors: Z
authors: Zhu
authors: Martin
authors: M
authors: Tepel
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000187:drug effects; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D004041:Dietary Fats; D004224:Diterpenes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D012333:RNA, Messenger; D011973:Receptors, LDL; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D025521:Tumor Suppressor Proteins; C024353:resiniferatoxin; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D002211:Capsaicin; D002118:Calcium