Particulate matter (PM), a major
air pollutant, may be associated with adverse cardiovascular effects.
Reactive oxygen species- (ROS-) dependent proinflammatory
cytokine production, such as
interleukin-6 (IL-6), is a possible underlying mechanism.
Carbon monoxide- (CO-) releasing molecule-2 (CORM-2) which liberates exogenous CO can exert many beneficial effects, particularly anti-
inflammation and
antioxidant effects. The purpose of this study was to explore the protective effects and underpinning mechanisms of
CORM-2 on PM-induced aorta
inflammation. Here, human aortic vascular smooth muscle cells (HASMCs) were utilized as in vitro models for the assessment of signaling pathways behind
CORM-2 activities against PM-induced inflammatory responses, including
Toll-like receptors (TLRs),
NADPH oxidase, ROS,
nuclear factor-kappa B (NF-κB), and
IL-6. The modulation of monocyte adherence and HASMC migration, that are two critical cellular events of inflammatory process, along with their regulators, including
intercellular adhesion molecule-1 (ICAM-1),
vascular cell adhesion molecule-1 (VCAM-1), and
matrix metalloproteinase-2 (MMP-2) and MMP-9, in response to PM by
CORM-2, were further evaluated. Finally, mice experiments under different conditions were conducted for the in vivo evaluation of
CORM-2 benefits on the expression of inflammatory molecules including
IL-6,
ICAM-1,
VCAM-1, MMP-2, and MMP-9. Our results found that PM could induce aorta
inflammation in vitro and in vivo, as evidenced by the increase of
IL-6 expression that was regulated by the TLR2 and TLR4/
NADPH oxidase/ROS/NF-κB signaling pathway, thereby promoting ICAM-1- and VCAM-1-dependent monocyte adhesion and MMP-2- and MMP-9-dependent HASMC migration. Importantly, our experimental models demonstrated that CORM-2-liberated CO effectively inhibited the whole identified PM-induced inflammatory cascade in HASMCs and tissues. In conclusion,
CORM-2 treatment may elicit multiple beneficial effects on inflammatory responses of aorta due to PM exposure, thereby providing therapeutic value in the context of inflammatory diseases of the cardiovascular system.