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: Linan Su, Yunrong Zhang, Kecheng He, Shujie Wei, Haifeng Pei, Qiang Wang, Dachun Yang, Yongjian Yang
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 65 Issue 1 Pg. 197-205.e2 (Jan 2017) ISSN: 1097-6809 [Electronic] United States
• PMID: 26947234 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Chemical References

• Calcium Chelating Agents
• Mitochondrial Proteins
• TRPV Cation Channels
• TRPV1 protein, human
• TRPV1 protein, mouse
• Egtazic Acid
• Adenosine Triphosphate
• GTP Phosphohydrolases
• MFN2 protein, human
• Mfn2 protein, mouse
• 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
• capsazepine
• Capsaicin

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Calcium Chelating Agents (pharmacology)
• Capsaicin (analogs & derivatives, pharmacology)
• Carotid Artery Injuries (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Egtazic Acid (analogs & derivatives, pharmacology)
• Endothelial Cells (drug effects, metabolism, pathology)
• GTP Phosphohydrolases (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hyperplasia
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice, Inbred C57BL
• Mice, Knockout
• Mitochondrial Proteins (genetics, metabolism)
• Neointima
• RNA Interference
• Re-Epithelialization (drug effects)
• Signal Transduction (drug effects)
• TRPV Cation Channels (agonists, deficiency, genetics, metabolism)
• Transfection