Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques

Abstract

demiologic studies have shown an association between exposure to ambient particulate air pollution Ͻ10 m in diameter (PM10) and increased cardiovascular morbidity and mortality. We previously showed that PM10 exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM10-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM10. Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM10 (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2Ј-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM10 caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 ␣-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM10 increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM10-induced progression of atherosclerosis. atherosclerosis; adhesion molecules EPIDEMIOLOGIC STUDIES have associated exposure to ambient particulate air pollution Ͻ10 m in diameter (PM 10

Understanding Human Illness and Death Following Exposure to Particulate Matter Air Pollution

“…Work done by our laboratory at the James Hogg Research Center showed structural changes in atherosclerotic plaques from Watanabe Heritable Hyperlipidemic (WHHL) rabbits exposed to PM 10 (Suwa et al, 2002;Tranfield et al, 2010;Yatera et al, 2008) and from ApoE -/-mice exposed to diesel exhaust (Bai et al, 2011). The observed changes were consistent with atherosclerotic plaques vulnerable to rupture.…”

Ultrastructural changes in atherosclerotic plaques following the instillation of airborne particulate matter into the lungs of rabbits

“…Rabbits were sacrificed at 42 and 46 weeks of age at the completion of a four-week exposure protocol. The rabbits used in the present study were also used in other investigations to address monocyte release from the bone marrow (20) and monocyte recruitment into atherosclerotic plaques (32).…”

“…The model used to test the hypothesis of the present study has been established in the James Hogg iCAPTURE Research Centre, Providence Heart + Lung Institute (Vancouver, British Columbia), and is well characterized with regard to both the local and the systemic response (20,26,32,36,37). Briefly, the experimental rabbits (n=8) were lightly anesthetized with 5% halo thane while 5 mg of EHC-93, suspended in 1 mL of sterile saline, was deposited just above the larynx using a blunt curved needle twice per week for four weeks.…”

“…For a more detailed discussion of the pulmonary and systemic response to PM 10 exposure, please refer to a recent review by Hogg and van Eeden (53). Our working hypothesis is that the cytokines released into the circulation lead to a systemic inflammatory response that follows PM 10 exposure (51) and activates the endothelium covering the atherosclerotic plaques (32). This endothelial activation could result in the release of the chemotactic stimuli responsible for the emigration of macrophage-derived foam cells from plaque cores, through the fibrous cap, across the endothelium and onto the lumen of the aorta.…”

Ambient particulate matter exposure and cardiovascular diseases: a focus on progenitor and stem cells

“…Indeed, PM exposure is able to significantly alter the function and responses of platelets both in vitro and in vivo including induction of Ca(2+) release, dense granule secretion and surface expression of platelet activation markers like P‐selectin expression, as well as aggregation, and change in the mean platelet volume 142, 143, 144, 145, 146. Particulate matter exposure/treatment has been shown to modify the function of monocytes significantly including inflammatory response and cytokine production, recruitment and mobilization, and transcriptional and translational modulations of gene expressions in monocytes 135, 136, 147, 148, 149, 150, 151, 152. Further studies are needed to determine the complex relations between PM exposure, monocyte and platelet function, and progenitor cells/SCs.…”