PMID- 33574976 OWN - NLM STAT- MEDLINE DCOM- 20210518 LR - 20240226 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2021 DP - 2021 TI - S-Nitroso-L-Cysteine Ameliorated Pulmonary Hypertension in the MCT-Induced Rats through Anti-ROS and Anti-Inflammatory Pathways. PG - 6621232 LID - 10.1155/2021/6621232 [doi] LID - 6621232 AB - Pulmonary hypertension (PH) is a progressive and life-threatening chronic disease in which increased pulmonary artery pressure (PAP) and pulmonary vasculature remodeling are prevalent. Inhaled nitric oxide (NO) has been used in newborns to decrease PAP in the clinic; however, the effects of NO endogenous derivatives, S-nitrosothiols (SNO), on PH are still unknown. We have reported that S-nitroso-L-cysteine (CSNO), one of the endogenous derivatives of NO, inhibited RhoA activity through oxidative nitrosation of its C16/20 residues, which may be beneficial for both vasodilation and remodeling. In this study, we presented data to show that inhaled CSNO attenuated PAP in the monocrotaline- (MCT-) induced PH rats and, moreover, improved right ventricular (RV) hypertrophy and fibrosis induced by RV overloaded pressure. In addition, aerosolized CSNO significantly inhibited the hyperactivation of signal transducers and activators of transduction 3 (STAT3) and extracellular regulated protein kinases (ERK) pathways in the lung of MCT-induced rats. CSNO also regulated the expression of smooth muscle contractile protein and improved aberrant endoplasmic reticulum (ER) stress and mitophagy in lung tissues following MCT induction. On the other hand, CSNO inhibited reactive oxygen species (ROS) production in vitro, which is induced by angiotensin II (AngII) as well as interleukin 6 (IL-6). In addition, CSNO inhibited excessive ER stress and mitophagy induced by AngII and IL-6 in vitro; finally, STAT3 and ERK phosphorylation was inhibited by CSNO in a concentration-dependent manner. Taken together, CSNO led to pulmonary artery relaxation and regulated pulmonary circulation remodeling through anti-ROS and anti-inflammatory pathways and may be used as a therapeutic option for PH treatment. CI - Copyright (c) 2021 Moran Wang et al. FAU - Wang, Moran AU - Wang M AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Luo, Pengcheng AU - Luo P AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Shi, Wei AU - Shi W AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Guo, Junyi AU - Guo J AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Huo, Shengqi AU - Huo S AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yan, Dan AU - Yan D AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Peng, Lulu AU - Peng L AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Cuntai AU - Zhang C AD - Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Lv, Jiagao AU - Lv J AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Lin, Li AU - Lin L AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Sheng AU - Li S AUID- ORCID: 0000-0002-2918-9164 AD - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20210128 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Reactive Oxygen Species) RN - 0 (S-Nitrosothiols) RN - 0 (STAT3 Transcription Factor) RN - 73077K8HYV (Monocrotaline) RN - 9007-34-5 (Collagen) RN - 926P2322P4 (S-nitrosocysteine) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - K848JZ4886 (Cysteine) SB - IM RIN - Oxid Med Cell Longev. 2023 Oct 11;2023:9781259. PMID: 37868726 MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use MH - Cell Line MH - Cell Movement/drug effects MH - Collagen/metabolism MH - Cysteine/*analogs & derivatives/pharmacology/therapeutic use MH - Endoplasmic Reticulum Stress/drug effects MH - Hemodynamics/drug effects MH - Hypertension, Pulmonary/complications/*drug therapy/physiopathology MH - Hypertrophy, Right Ventricular/complications/drug therapy/physiopathology MH - Lung/drug effects/pathology MH - MAP Kinase Signaling System/drug effects MH - Male MH - Matrix Metalloproteinases/metabolism MH - Mitophagy/drug effects MH - Monocrotaline MH - Muscle Contraction/drug effects MH - Muscle, Smooth/drug effects/physiopathology MH - Oxidative Stress/drug effects MH - Phosphorylation/drug effects MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/*metabolism MH - S-Nitrosothiols/pharmacology/*therapeutic use MH - STAT3 Transcription Factor/metabolism MH - Vascular Remodeling/drug effects MH - Wound Healing/drug effects MH - Rats PMC - PMC7861928 COIS- The authors declare that there is no conflict of interest. EDAT- 2021/02/13 06:00 MHDA- 2021/05/19 06:00 PMCR- 2021/01/28 CRDT- 2021/02/12 06:08 PHST- 2020/11/09 00:00 [received] PHST- 2020/12/21 00:00 [revised] PHST- 2021/01/07 00:00 [accepted] PHST- 2021/02/12 06:08 [entrez] PHST- 2021/02/13 06:00 [pubmed] PHST- 2021/05/19 06:00 [medline] PHST- 2021/01/28 00:00 [pmc-release] AID - 10.1155/2021/6621232 [doi] PST - epublish SO - Oxid Med Cell Longev. 2021 Jan 28;2021:6621232. doi: 10.1155/2021/6621232. eCollection 2021.