TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes

• Published in: Scientific reports 2021-07, Vol.11 (1), p.14689-14689, Article 14689
• Main Authors: Sattler, Katherine, El-Battrawy, Ibrahim, Cyganek, Lukas, Lang, Siegfried, Lan, Huan, Li, Xin, Zhao, Zhihan, Utikal, Jochen, Wieland, Thomas, Borggrefe, Martin, Zhou, Xiaobo, Akin, Ibrahim
• Format: Article
• Language: English
• Subjects: 631/80/304; 692/4019/592; Capsaicin; Capsaicin receptors; Capsazepine; Cardiomyocytes; Cardiovascular system; Electrophysiology; Enzyme-linked immunosorbent assay; Humanities and Social Sciences; Immunofluorescence; Inflammation; Interleukin 6; Internalization; Lipopolysaccharides; mRNA; multidisciplinary; Phosphorylation; Pluripotency; Science; Science (multidisciplinary); Stem cells; Transient receptor potential proteins; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-93958-3

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.