TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway.
Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway.



Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca2+-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation. NO metabolites, protein expression, and inflammatory molecules were evaluated by Griess assay and immune assay-based multiplex analysis, respectively. Monocyte adhesion was determined by measuring the fluorescently labeled human monocytes attached to LPS-stimulated ECs.



In HUVECs, treatment with CAP increased NO production, and CAP-induced NO production was accompanied by increased eNOSser1177phosphorylation. Additionally, CAP attenuated LPS-induced cytokine and chemokine production, adhesion molecule expression, activation of NF-κB, and monocyte adhesion in HUVECs, and these effects were abrogated by the inhibition of TRPV1, NOS, or Ca2+-dependent PI3K/Akt pathway. Moreover, these protective actions of TRPV1 were also observed in renal MVECs isolated from DOCA-salt hypertensive mice.



Our results indicate that TRPV1 activation suppresses the inflammatory response of ECs via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway, the protective effects are also documented in ECs derived from salt-sensitive hypertensive mice.
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China. Electronic address: wangyp8@163.com.
Youping
Y
Wang
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China.
Lin
L
Cui
Department of Pharmacology and Toxicology, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
Hui
H
Xu
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China.
Suxiao
S
Liu
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China.
Feiyun
F
Zhu
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China.
Fengna
F
Yan
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China.
Si
S
Shen
Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China. Electronic address: zhumingjun317@163.com.
Mingjun
M
Zhu
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000819:agonists* / Q000378:metabolism
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
Endothelial cell; Endothelial nitric oxide synthase; Hypertension; Inflammation; Nitric oxide; Transient receptor potential vanilloid type 1 channel