Abstract
BackgroundCigarette smoking is a leading cause of mortality and morbidity and is associated with cardiovascular disease via contributory processes such as endothelial dysfunction, inflammation and thrombosis. Cigarette smoke both contains and stimulates the production of cellular oxidants and it may also promote vascular inflammation. Osteopontin is a non-collagenous matrix protein first identified in bone and there is increasing evidence for its role in inflammation and cardiovascular disease via its action as a soluble cytokine.MethodsIn this study we have examined the mechanisms underlying the expression of osteopontin in human vascular endothelial cells in vitro following exposure to cigarette smoke particulate matter (PM), using PCR, electrochemiluminescence, immunostaining and Western blotting. We further determined if serum osteopontin levels changed in humans who quit smoking.ResultsNon-cytotoxic concentrations of PM increased osteopontin levels in cultured human endothelial cells and this effect was reduced in the presence of ascorbate, suggesting a role for oxidants in the response to PM. However, oxidant production played no role in the PM-evoked induction MMP-3, an enzyme which cleaves osteopontin. In smokers who quit smoking for 5 days, serum osteopontin levels were significantly lowered compared to those measured prior to smoking cessation.ConclusionsIn vitro cigarette smoke extract exposure induced osteopontin expression in human endothelial cells in an oxidative stress-dependent manner, which may involve MMP-3 cleavage. In humans, serum osteopontin was decreased with short-term smoking cessation. Endothelial-derived osteopontin may contribute to inflammation in smokers, and may also contribute to atherosclerosis and cardiovascular disease-related processes.
Highlights
Cigarette smoking is a leading cause of mortality and morbidity and is associated with cardiovascular disease via contributory processes such as endothelial dysfunction, inflammation and thrombosis
Concentration-dependent cytotoxicity of particulate matter (PM) in endothelial cells To determine a non-cytotoxic range of cigarette smoke PM concentrations, neutral red viability assays were used to determine the cytotoxicity of PM exposure (0 to 200 μg/ml for 24 h) in human umbilical vein endothelial cells (HUVECs)
PM-induced expression of matrix metalloproteinases (MMPs)-3 is independent of oxidative stress Since PM caused an increase in osteopontin expression via an oxidative stress-sensitive mechanism which may involve MMP-3 cleavage of osteopontin, we examined MMP-3 expression in Human umbilical vein endothelial cells (HUVECs) exposed to PM
Summary
Cigarette smoking is a leading cause of mortality and morbidity and is associated with cardiovascular disease via contributory processes such as endothelial dysfunction, inflammation and thrombosis. Cigarette smoke both contains and stimulates the production of cellular oxidants and it may promote vascular inflammation. Osteopontin is a non-collagenous matrix protein first identified in bone and there is increasing evidence for its role in inflammation and cardiovascular disease via its action as a soluble cytokine. Cigarette smoking has a long-standing association with cardiovascular disease and there is a wealth of evidence concerning the effects of smoking on key pathological processes such as vascular injury, Osteopontin is a non-collagenous matricellular protein [6] which was first identified as a component of bone and is involved in bone formation and calcification [7]. Osteopontin expression has been detected in angiogenic endothelial cells, smooth muscle cells and macrophages from atherosclerotic plaques, suggestive of a role in lesion remodelling [8]
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