PMID- 25680906 OWN - NLM STAT- MEDLINE DCOM- 20160302 LR - 20161125 IS - 1095-8584 (Electronic) IS - 0022-2828 (Linking) VI - 81 DP - 2015 Apr TI - Macrophage inflammasome mediates hyperhomocysteinemia-aggravated abdominal aortic aneurysm. PG - 96-106 LID - S0022-2828(15)00042-5 [pii] LID - 10.1016/j.yjmcc.2015.02.005 [doi] AB - Abdominal aortic aneurysm (AAA) is a serious vascular disease with high mortality. Our previous study suggested that hyperhomocysteinemia (HHcy) exaggerates the occurrence of AAA. Here, we investigated whether macrophage inflammasome is involved in HHcy-aggravated AAA formation. Two independent HHcy-aggravated AAA models, perivascular calcium phosphate-treated C57BL/6 mice and angiotensin II (Ang II)-infused apolipoprotein E-deficient (ApoE(-/-)) mice were used. NLPR3, caspase 1, and interleukin-1beta (IL-1beta) levels were higher in aneurysmal lesions of both HHcy models compared to controls, preferentially in macrophages. Similarly, macrophage inflammasome activation was observed in vitro. Folic acid administration reversed the HHcy-accelerated AAA, with ameliorated activation of inflammasome in the tunica adventitia. Lentiviral silencing of NLRP3 significantly ameliorated HHcy-aggravated AAA formation. We observed increased mitochondrial production of reactive oxygen species (ROS) and energy switch from oxidative phosphorylation to glycolysis with excess Hcy in macrophages. Blocking mitochondrial ROS production in macrophages abolished inflammasome activation. Our study highlights the potential importance of macrophage inflammasome in the pathogenesis and development of HHcy-aggravated AAA. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Sun, Weiliang AU - Sun W AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Pang, Yanli AU - Pang Y AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People's Republic of China. FAU - Liu, Ziyi AU - Liu Z AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Sun, Lulu AU - Sun L AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Liu, Bo AU - Liu B AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Xu, Mingjiang AU - Xu M AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Dong, Yongqiang AU - Dong Y AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Feng, Juan AU - Feng J AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Jiang, Changtao AU - Jiang C AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. FAU - Kong, Wei AU - Kong W AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. Electronic address: kongw@bjmu.edu.cn. FAU - Wang, Xian AU - Wang X AD - Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. Electronic address: xwang@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150211 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Apolipoproteins E) RN - 0 (Calcium Phosphates) RN - 0 (Carrier Proteins) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (RNA, Small Interfering) RN - 0 (Reactive Oxygen Species) RN - 935E97BOY8 (Folic Acid) RN - 97Z1WI3NDX (calcium phosphate) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Adventitia/drug effects/metabolism/pathology MH - Animals MH - Aortic Aneurysm, Abdominal/chemically induced/complications/*metabolism/prevention & control MH - Apolipoproteins E/deficiency/genetics MH - Calcium Phosphates/adverse effects MH - Carrier Proteins/antagonists & inhibitors/genetics/*metabolism MH - Caspase 1/genetics/metabolism MH - Disease Models, Animal MH - Fibroblasts/drug effects/metabolism/pathology MH - Folic Acid/pharmacology MH - Gene Expression MH - Hyperhomocysteinemia/chemically induced/complications/*metabolism/prevention & control MH - Inflammasomes/drug effects/*metabolism MH - Interleukin-1beta/genetics/metabolism MH - Macrophage Activation/drug effects MH - Macrophages/drug effects/*metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mitochondria/drug effects/metabolism/pathology MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - Primary Cell Culture MH - RNA, Small Interfering/genetics/metabolism MH - Rats MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Abdominal aortic aneurysm OT - Hyperhomocysteinemia OT - Inflammasome OT - Macrophage OT - Mitochondrial reactive oxygen species EDAT- 2015/02/15 06:00 MHDA- 2016/03/05 06:00 CRDT- 2015/02/15 06:00 PHST- 2015/01/06 00:00 [received] PHST- 2015/02/02 00:00 [revised] PHST- 2015/02/03 00:00 [accepted] PHST- 2015/02/15 06:00 [entrez] PHST- 2015/02/15 06:00 [pubmed] PHST- 2016/03/05 06:00 [medline] AID - S0022-2828(15)00042-5 [pii] AID - 10.1016/j.yjmcc.2015.02.005 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2015 Apr;81:96-106. doi: 10.1016/j.yjmcc.2015.02.005. Epub 2015 Feb 11.