Concentrated Ambient [Formula: see text] Induced Inflammation and Endothelial Dysfunction in a Murine Model of Neural IKK2 Deficiency

BACKGROUND: Exposure to ambient fine particulate matter ([Formula: see text]) is associated with cardiovascular mortality, but underlying pathophysiologic mechanisms are not fully understood. Hypothalamic inflammation, characterized by the activation of Inhibitor kappaB kinase 2/Nuclear factor kappaB ([Formula: see text]) signaling pathway, may play an important role in the pathogenesis of cardiovascular diseases. We recently demonstrated that hypothalamic inflammation is increased in mice exposed to concentrated ambient [Formula: see text] (CAP). OBJECTIVES: In the present study, we used a neuron-specific IKK2 knockout mouse model to examine the role of neural IKK2 expression and hypothalamic inflammation in the pathophysiologic effects of [Formula: see text]. METHODS: We assessed inflammatory and vascular responses in [Formula: see text] ([Formula: see text]) and littermate [Formula: see text] (control) mice after 4 mo of exposure to filtered air (FA) or CAP. RESULTS: CAP exposure was associated with significantly higher tumor necrosis factor- [Formula: see text] [Formula: see text] and interleukin (IL)-6 mRNA in the hypothalamus of control mice, but not [Formula: see text] mice. In addition, CAP exposure–induced increases in bronchoalveolar lavage fluid (BALF) leukocytes, pulmonary macrophage infiltration and IL-6 expression, plasma [Formula: see text] and [Formula: see text] levels, adipose macrophage infiltration and [Formula: see text] expression, and endothelial dysfunction were reduced or absent in [Formula: see text] mice compared with controls. CONCLUSIONS: Our findings support a role of neural IKK2 in CAP exposure–induced local and systemic pro-inflammatory cytokine expression, pulmonary and adipose inflammation, and endothelial dysfunction, thus providing insight into pathophysiologic mechanisms that may mediate effects of [Formula: see text] exposure. https://doi.org/10.1289/EHP2311