TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes
The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 July 2021
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| In: |
Scientific reports
Year: 2021, Volume: 11, Pages: 1-12 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-021-93958-3 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41598-021-93958-3 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-021-93958-3 
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| Author Notes: | Katherine Sattler, Ibrahim El-Battrawy, Lukas Cyganek, Siegfried Lang, Huan Lan, Xin Li, Zhihan Zhao, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiaobo Zhou and Ibrahim Akin |
| Summary: | The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (hiPSC-CM) from 4 healthy donors were incubated with lipopolysaccharides (LPS, 6 h), TRPV1 agonist capsaicin (CAP, 20 min) or the antagonist capsazepine (CPZ, 20 min). TRPV1 expression was studied by PCR and western blotting. TRPV1 internalization was analyzed by immunofluorescence. Interleukin-6 (IL-6) secretion and phosphorylation of JNK, p38 and ERK were determined by ELISA. TRPV1-associated ion channel current was measured by patch clamp. TRPV1-mRNA and -protein were expressed in hiPSC-CM. TRPV1 was localized in the plasma membrane. LPS significantly increased secretion of IL-6 by 2.3-fold, which was prevented by pre-incubation with CPZ. LPS induced TRPV1 internalization. Phosphorylation levels of ERK, p38 or JNK were not altered by TRPV1 stimulation or inhibition. LPS and IL-6 significantly lowered TRPV1-mediated ion channel current. TRPV1 mediates the LPS-induced inflammation in cardiomyocytes, associated with changes of cellular electrophysiology. LPS-induced inflammation results in TRPV1 internalization. Further studies have to examine the underlying pathways and the clinical relevance of these findings. |
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| Item Description: | Published: 19 July 2021 Gesehen am 31.05.2022 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-021-93958-3 |