Zhongguo Ren1, Rong Hu2. 1. Department of Anesthesiology, The People's Hospital of China Three Gorges University, Yichang, China. 2. Department of Geriatrics, The People's Hospital of China Three Gorges University, Yichang, China.
Abstract
BACKGROUND: Propofol (PPF) overdose is a rare but lethal condition, which may lead to severe cardiac failure. In this study, we established an in vitro PPF-induced cardiac cytotoxicity model, and investigate the functional role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6). METHODS: Human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) were exposed to PPF in vitro. PPF-induced cytotoxic effects were measured. PPF-induced SNHG6 expression change in HiPSC-CMs were monitored by qRT-PCR. SNHG6 was downregulated in HiPSC-CMs to examine its role in PPF-induced cardiac cytotoxicity. The expression of competing endogenous RNA (ceRNA) candidate of SNHG6, human microRNA-186-5p (hsa-miR-186-5p) was also investigated in PPF-exposed HiPSC-CMs. Functions of hsa-miR-186-5p were further investigated in PPF-exposed and SNHG6-downregulated HiPSC-CMs. RESULTS: PPF induced significant cytotoxicity, as well as SNHG6 upregulation in HiPSC-CMs. SNHG6 downregulation had rescuing effects on PPF-induced cardiac cytotoxicity. Dual-luciferase activity assay confirmed that hsa-miR-186-5p was the ceRNA candidate of SNHG6. QRT-PCR showed hsa-miR-186-5p expression was reversely correlated with SNHG6 in PPF-exposed HiPSC-CMs. Suppressing hsa-miR-186-5p reduced the rescuing effects of SNHG6-downregulation on PPF-induced cardiac cytotoxicity. CONCLUSIONS: SNHG6/hsa-miR-186-5p can modulate PPF-induced cardiac cytotoxicity in HiPSC-CMs, and thus may be a future drug target to prevent PPF infusion syndrome. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.
BACKGROUND: Propofol (PPF) overdose is a rare but lethal condition, which may lead to severe cardiac failure. In this study, we established an in vitro PPF-induced cardiac cytotoxicity model, and investigate the functional role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6). METHODS: Human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) were exposed to PPF in vitro. PPF-induced cytotoxic effects were measured. PPF-induced SNHG6 expression change in HiPSC-CMs were monitored by qRT-PCR. SNHG6 was downregulated in HiPSC-CMs to examine its role in PPF-induced cardiac cytotoxicity. The expression of competing endogenous RNA (ceRNA) candidate of SNHG6, human microRNA-186-5p (hsa-miR-186-5p) was also investigated in PPF-exposed HiPSC-CMs. Functions of hsa-miR-186-5p were further investigated in PPF-exposed and SNHG6-downregulated HiPSC-CMs. RESULTS: PPF induced significant cytotoxicity, as well as SNHG6 upregulation in HiPSC-CMs. SNHG6 downregulation had rescuing effects on PPF-induced cardiac cytotoxicity. Dual-luciferase activity assay confirmed that hsa-miR-186-5p was the ceRNA candidate of SNHG6. QRT-PCR showed hsa-miR-186-5p expression was reversely correlated with SNHG6 in PPF-exposed HiPSC-CMs. Suppressing hsa-miR-186-5p reduced the rescuing effects of SNHG6-downregulation on PPF-induced cardiac cytotoxicity. CONCLUSIONS: SNHG6/hsa-miR-186-5p can modulate PPF-induced cardiac cytotoxicity in HiPSC-CMs, and thus may be a future drug target to prevent PPF infusion syndrome. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.
Authors: Lei Yang; Mark H Soonpaa; Eric D Adler; Torsten K Roepke; Steven J Kattman; Marion Kennedy; Els Henckaerts; Kristina Bonham; Geoffrey W Abbott; R Michael Linden; Loren J Field; Gordon M Keller Journal: Nature Date: 2008-04-23 Impact factor: 49.962