title: IKK inhibition prevents PM2.5-exacerbated cardiac injury in mice with type 2 diabetes.
abstract: Epidemiological studies have found that individuals with diabetes mellitus (DM) display an increased susceptibility for adverse cardiovascular outcomes when exposed to air pollution. This study was conducted to explore the potential mechanism linking ambient fine particles (PM2.5) and heart injury in a Type 2 DM (T2DM) animal model. The KKay mouse, an animal model of T2DM, was exposed to concentrated ambient PM2.5 or filtered air for 8 weeks via a versatile aerosol exposure and concentrator system. Simultaneously, an inhibitor of IκB kinase-2 (IKK-â) (IMD-0354), which is a blocker of nuclear factor κB (NF-κB) nuclear translocation, was administrated by intracerebroventricular injection (ICV) to regulate the NF-êB pathway. The results showed that ambient PM2.5 induced the increase of, NF-êB, cyclooxygenase-2 (COX-2) and mitogen activated protein kinase (MAPK) expression in cardiac tissue, and that IMD-0354 could alleviate the inflammatory injury. The results suggested that the NF-êB pathway plays an important role in mediating the PM2.5-induced cardiovascular injury in the T2DM model. Inhibiting NFκB may be a therapeutic option in air-pollution-exacerbated cardiovascular injury in diabetes mellitus.
authors.affiliation: Department of Environment Health, School of Public Health and the Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China; Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA.
authors.forename: Jinzhuo
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Tse-yao
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Environment Health, School of Public Health and the Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Kan
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: sun.224@osu.edu.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000139:chemically induced*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058847:Inflammasomes; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D001549:Benzamides; D058847:Inflammasomes; D016328:NF-kappa B; D052638:Particulate Matter; C492919:N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Cardiovascular diseases; Diabetes mellitus; Fine particles; NFκB