Abstract
Exposure to urban air pollution is an independent risk factor for increased cardiovascular diseases. Heat shock protein 70 (HSP70) has been implicated in the pathogenesis of vascular dysfunction and cardiovascular diseases. This study has been designed to determine whether inhalation of urban air induces HSP70 expression in the lung and blood as well as the association of HSP70 and air pollution-induced vascular dysfunction. Apolipoprotein E (Apo-E) deficient mice were exposed to diesel exhaust (DE) either acutely (3 days, 200 or 400 µg/m3 for 6 h/day) or chronically (7 weeks, 200 or 400 µg/m3 for 6 h/day). HSP70 was measured in the lung using immunohistochemistry, and in the plasma by ELISA. Abdominal aorta rings were used to determine vascular functional responses. Chronic DE-exposure increased the fraction of HSP70 positive alveolar macrophages (AM) that was related to the fraction of particle-laden AM in the lung (r2 = 0.48, p < 0.01). Chronic DE-exposure increased plasma HSP70 levels and reduced blood vessel responses to phenylephrine (PE). The fraction of particle-laden HSP70 positive AM was associated with abnormal vasoconstriction responses to PE induced by DE-exposure (r2 = 0.12, p = 0.02). Our results show that chronic inhalation of DE increases HSP70 expression in the lung and systemic circulation, and we postulate that HSP70 possibly contributes to air pollution induced vascular dysfunction and cardiovascular diseases.
Acknowledgments
We gratefully thank to Amrit Samra, Beth Whalen and Kumiko Kido for technical supports.
Declaration of interest
SVE is a Senior Scholars with the Michael Smith Foundation for Medical Research, a career Investigator of the American Lung Association and the CIHR/GSK professor in COPD. NB is a recipient of a scholarship from both the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Michael Smith Foundation for Health Research and Heart and Stroke Foundation of Canada. This work was supported by the BC Lung Association and the NIH. The authors report no conflicts of interests.