CD36 Mediates Endothelial Dysfunction Downstream of Circulating Factors Induced by O3 Exposure

Inhaled pollutants induce the release of vasoactive factors into the systemic circulation, but little information is available regarding the nature of these factors or their receptors. The pattern recognition receptor CD36 interacts with many damage-related circulating molecules, leading to activation of endothelial cells and promoting vascular inflammation; therefore, we hypothesized that CD36 plays a pivotal role in mediating cross talk between inhaled ozone (O-3)-induced circulating factors and systemic vascular dysfunction. O-3 exposure (1 ppm 4h) induced lung inflammation in wild-type (WT) mice, which was absent in the CD36 deficient (CD36(/)) mice. Acetylcholine (ACh)-evoked vasorelaxation was impaired in isolated aortas from O-3-exposed WT mice but not in vessels from CD36(/) mice. To delineate whether vascular impairments were caused by lung inflammation or CD36-mediated generation of circulating factors, nave aortas were treated with diluted serum from control or O-3-exposed WT mice, which recapitulated the impairments of vasorelaxation observed after inhalation exposures. Aortas from CD36(/) mice were insensitive to the effects of O-3-induced circulating factors, with robust vasorelaxation responses in the presence of serum from O-3-exposed WT mice. Lung inflammation was not a requirement for production of circulating vasoactive factors, as serum from O-3-exposed CD36(/) mice could inhibit vasorelaxation in nave WT aortas. These results suggest that O-3 inhalation induces the release of circulating bioactive factors capable of impairing vasorelaxation to ACh via a CD36-dependent signaling mechanism. Although lung inflammatory and systemic vascular effects were both dependent on CD36, the presence of circulating factors appears to be independent of CD36 and inflammatory responses.