First Department of Medicine, Faculty of Medicine, University Medical Center Mannheim (UMM), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
European Center for AngioScience (ECAS), Mannheim, Germany.
Sci Rep. 2021 Jul 19;11(1):14689. 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.
瞬时受体电位香草素 1 型（TRPV1）是非选择性阳离子通道，广泛表达于心血管系统。近期的研究证据表明 TRPV1 在炎症反应中发挥作用。然而，TRPV1 在心肌炎症中的作用尚未明确。我们使用 4 位健康供体的人诱导多能干细胞（hiPSC）分化的心肌细胞（hiPSC-CM），与脂多糖（LPS，6 h）、TRPV1 激动剂辣椒素（CAP，20 min）或拮抗剂辣椒平（CPZ，20 min）孵育。通过 PCR 和 Western blot 检测 TRPV1 的表达；通过免疫荧光分析 TRPV1 的内化；通过 ELISA 检测白细胞介素-6（IL-6）的分泌和 JNK、p38 和 ERK 的磷酸化；通过膜片钳技术测量 TRPV1 相关的离子通道电流。TRPV1-mRNA 和蛋白在 hiPSC-CM 中表达，TRPV1 定位于细胞膜。LPS 使 IL-6 的分泌增加了 2.3 倍，CPZ 预处理可阻止这种增加。LPS 诱导 TRPV1 内化。TRPV1 的刺激或抑制均不改变 ERK、p38 或 JNK 的磷酸化水平。LPS 和 IL-6 显著降低 TRPV1 介导的离子通道电流。TRPV1 介导 LPS 诱导的心肌细胞炎症，与细胞电生理变化相关。LPS 诱导的炎症导致 TRPV1 内化。进一步的研究需要探索这些发现的潜在途径和临床意义。
