The role of the lectin-like oxLDL receptor (LOX-1) in traffic-generated air pollution exposure-mediated alteration of the brain microvasculature in Apolipoprotein (Apo) E knockout mice

Abstract

Recent studies have shown a strong correlation between air pollution-exposure and detrimental outcomes in the central nervous system, including alterations in blood brain barrier (BBB) integrity, neuroinflammation, and neurodegeneration. However, the mechanisms mediating these pathologies have not yet been fully elucidated. We have previously reported that exposure to traffic-generated air pollution results in increased circulating oxidized low-density lipoprotein (oxLDL), associated with alterations in BBB integrity, in atherosclerotic Apolipoprotein E null (ApoE^−/−) mice. Thus, we investigated the role of the lectin-like oxLDL receptor (LOX)-1 in mediating these deleterious effects in ApoE^−/− mice exposed to a mixture of gasoline and diesel engine exhaust (MVE: 100 PM µg/m³) for 6 h/d, 7d/week, for 30 d by inhalation. Concurrent with exposures, a subset of mice were treated with neutralizing antibodies to LOX-1 (LOX-1 Ab) i.p., or IgG (control) i.p., every other day during exposures. Resulting brain microvascular integrity, tight junction (TJ) protein expression, matrix metalloproteinase (MMP)-9/-2 activity, ROS, and markers of cellular adhesion and monocyte/macrophage sequestration were assessed. MVE-exposure resulted in decreased BBB integrity and alterations in microvascular TJ protein expression, associated with increased LOX-1 expression, MMP-9/-2 activities, and lipid peroxidation, each of which was attenuated with LOX-1 Ab treatment. Furthermore, MVE-exposure induced cerebral microvascular ROS and adhesion molecules, expression of which was not normalized through LOX-1 Ab-treatment. Such findings suggest that alterations in brain microvascular structure and integrity observed with MVE-exposure may be mediated, at least in part, via LOX-1 signaling.

Keywords:

• Air pollution
• LOX-1
• oxLDL
• BBB
• MMP-9
• inflammation

Acknowledgements

We would like to thank the Chemistry and Inhalation Exposure group, in the Environmental Respiratory Health Program, at Lovelace Biomedical and Environmental Research Institute for the characterization and monitoring of the animal exposures.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by National Institute of Environmental Health Sciences (NIEHS) at National Institute of Health [5R00ES016586 to A.K.L.] and University of North Texas Research Initiation Grant (RIG) [GA93601 to A.K.L] and Environmental Protection Agency Center Grant RD-83479601 [Project 3 to A.K.L., coInvestigator and Project 2 to J.D.M., coPI] for the animal exposures. However, the authors declare no financial gains to these entities associated with this publication.