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

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.

The study is to explore the potential mechanism linking ambient fine particles (PM2.5) and heart injury in type 2 diabetes mellitus (T2DM) animal model. The results showed that PM2.5 induced the increase of NFκB and IKK-β in myocardium of mice with DM. More importantly, IMD-0354, a blocker of NFκB, could alleviate the protein expressions of NFκB and IKK-β, suggesting that ambient PM2.5-induced cardiac injury is potentially associated with the NF-κB pathway-mediated cardiac inflammation.Figure optionsDownload as PowerPoint slide