title: CD36 mediates endothelial dysfunction downstream of circulating factors induced by O3 exposure.
abstract: 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 (O3)-induced circulating factors and systemic vascular dysfunction. O3 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 O3-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, naïve aortas were treated with diluted serum from control or O3-exposed WT mice, which recapitulated the impairments of vasorelaxation observed after inhalation exposures. Aortas from CD36(-/-) mice were insensitive to the effects of O3-induced circulating factors, with robust vasorelaxation responses in the presence of serum from O3-exposed WT mice. Lung inflammation was not a requirement for production of circulating vasoactive factors, as serum from O3-exposed CD36(-/-) mice could inhibit vasorelaxation in naïve WT aortas. These results suggest that O3 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.
authors: Department of Pharmaceutical Sciences, University of New Mexico College of Pharmacy, Albuquerque, New Mexico 87131, USA. srobertson@salud.unm.edu
authors: Sarah
authors: S
authors: Robertson
authors: Elizabeth S
authors: ES
authors: Colombo
authors: Selita N
authors: SN
authors: Lucas
authors: Pamela R
authors: PR
authors: Hall
authors: Maria
authors: M
authors: Febbraio
authors: Michael L
authors: ML
authors: Paffett
authors: Matthew J
authors: MJ
authors: Campen
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018955:CD36 Antigens / Q000276:immunology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D019570:Inhalation Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*
chemical_list: D018955:CD36 Antigens; D010126:Ozone
keywords: CD36; air pollution; endothelial; inflammation; ozone; pattern recognition receptor; scavenger receptor.; vascular; vasorelaxation
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