Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis

Cardiovasc Res. 2011 Dec 1;92(3):504-13. doi: 10.1093/cvr/cvr245. Epub 2011 Sep 9.

Abstract

Aims: 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.

Methods and 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.

Conclusion: Activation of TRPV1 may be a novel therapeutic tool to attenuate atherosclerosis caused by a high-fat diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Blotting, Western
  • Calcineurin / metabolism
  • Calcium / metabolism
  • Capsaicin / pharmacology*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dietary Fats / administration & dosage
  • Dietary Fats / metabolism*
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Immunohistochemistry
  • Lipid Metabolism / drug effects
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Receptors, LDL / metabolism
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / deficiency
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Time Factors
  • Tumor Suppressor Proteins / metabolism

Substances

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins E
  • Dietary Fats
  • Diterpenes
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Lrp1 protein, mouse
  • RNA, Messenger
  • Receptors, LDL
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Tumor Suppressor Proteins
  • resiniferatoxin
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin
  • Capsaicin
  • Calcium