سمیت استنشاق شبانه روزی آلودگی محیط زیست هوای آلوده شده برای ارائه یک سابقه Circadian Toxicity of Environmental Pollution. Inhalation of polluted air to give a precedent

Introduction Recent research suggest that urbanization, accompanied by migration to more polluted areas (light [1], and air [2] pollution) and our modern 24 h lifestyle (35% adults sleep less than the recommended 7-8 h [3]) could be significant factors fueling into the development of CVD and T2D worldwide [4]. Exposure to environmental light [1], air [2], water [5], and food [6] pollution are a major health concern and with intensified industrialization and urbanization [7], its disease burden is likely to increase in the future. For instance, both, exposure to polluted air as well as changes in the day/night cycle have been described to increase the susceptibility for cardiovascular and metabolic injury. Exposure to ambient air pollution is one of the leading causes of death world-wide that has been linked to 7 million premature deaths per year [2]. Ambient air pollution is a complex mixture of gaseous (i.e. carbon monoxide and dioxide, ozone, nitric oxide, sulfur- and nitrogen dioxide), volatile (i.e. hydrocarbons, aldehydes) and particulate matter (PM) components derived from various sources such as industry, traffic, farming, mining, wildfires, volcano eruptions, cigarette smoke, and wood stove burning [8]. While exposure to air pollution increases the risk of many diseases, most (60-80%) premature mortality associated with high levels of particulate matter (PM) air pollution is due to cardiovascular causes [9]. Acute exposure to increased levels of ambient PM increases the risk of acute myocardial infarction, arrhythmias, and stroke [9]. Chronically, exposure to PM contributes to lung injury, increases blood pressure and atherosclerotic lesion formation, and induces cardiac remodeling [9-11]. Both experimental and epidemiological data show that exposure to fine particulate matter (PM2.5) air pollution affects systemic insulin sensitivity in human and mice [12-14] and increases the risk for obesity and T2D [15,16]. Although the specific mechanism(s) of particle-induced cardiovascular and metabolic injury is ambiguous, it has been suggested that inhaled PM affects cardiovascular and metabolic health by either inducing oxidative stress and inflammation or stimulating sensory receptors in the lung that then extend systemically. In addition it has been suggested that ultrafine/nanosized particles or soluble particle constituents could enter the bloodstream and affect cardiovascular and metabolic health by direct interactions (Fig. 1) [8]. This is supported by studies that show for instance the critical role of oxidative stress in mediating PMinduced vascular and metabolic dysfunction [17,18] and our recent studies that show that averting pulmonary oxidative stress prevented PM2.5-induced vascular inflammation and insulin resistance and restored endothelial progenitor cell number and function [13,19].