IKK inhibition prevents PM2.5-exacerbated cardiac injury in mice with type 2 diabetes

Jinzhuo Zhao; Cuiqing Liu; Yuntao Bai; Tse-yao Wang; Haidong Kan; Qinghua Sun

doi:10.1016/j.jes.2014.10.018

IKK inhibition prevents PM2.5-exacerbated cardiac injury in mice with type 2 diabetes

J Environ Sci (China). 2015 May 1:31:98-103. doi: 10.1016/j.jes.2014.10.018. Epub 2015 Mar 25.

Authors

Jinzhuo Zhao¹, Cuiqing Liu², Yuntao Bai³, Tse-yao Wang³, Haidong Kan⁴, Qinghua Sun⁵

Affiliations

¹ 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.
² Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
³ 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.
⁴ Department of Environment Health, School of Public Health and the Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.
⁵ 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.

PMID: 25968264
DOI: 10.1016/j.jes.2014.10.018

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.

Keywords: Cardiovascular diseases; Diabetes mellitus; Fine particles; NFκB.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Air Pollutants / toxicity*
Animals
Benzamides / pharmacology
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism
Diabetes Mellitus, Type 2
Gene Expression Regulation
Heart Diseases / chemically induced*
I-kappa B Kinase / antagonists & inhibitors*
I-kappa B Kinase / metabolism
Inflammasomes
Mice
Mitogen-Activated Protein Kinase Kinases / genetics
Mitogen-Activated Protein Kinase Kinases / metabolism
NF-kappa B / metabolism
Particulate Matter / toxicity*

Substances

Air Pollutants
Benzamides
Inflammasomes
NF-kappa B
Particulate Matter
N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
Cyclooxygenase 2
I-kappa B Kinase
Mitogen-Activated Protein Kinase Kinases

Grants and funding

R01ES018900/ES/NIEHS NIH HHS/United States