nitrogen-dioxide and Arteriosclerosis

Long-term exposure to ambient air pollution has recently been linked to atherosclerosis and cardiovascular events. There are, however, very limited data in healthy young people. We examined the association between air pollutants and indicators of vascular damage in a cohort of young adults.. We used data from the Atherosclerosis Risk in Young Adults study. We estimated exposure to nitrogen dioxide (NO2), particulate matter less than 2.5 microm in aerodynamic diameter (PM2.5), black smoke, sulfur dioxide (SO2), and various traffic indicators for participants' 2000 home addresses. Exposure for the year 2000 was estimated by land-use regression models incorporating regional background annual air pollution levels, land-use variables, population densities, and traffic intensities on nearby roads. Outcomes were common carotid artery intima-media thickness (n = 745), aortic pulse wave velocity (n = 524), and augmentation index (n = 729).. Exposure contrasts were substantial for NO2, SO2, and black smoke (5th-95th percentiles = 19.7 to 44.9, 2.5 to 5.2, and 8.6 to 19.4 microg/m3, respectively) and smaller for PM2.5 (16.5 to 19.9 microg/m3). The variability of carotid artery intima-media thickness was less than for pulse wave velocity and especially augmentation index (5-95th percentiles = 0.42 to 0.58 mm, 4.9 to 7.4 m/s and -12.3% to 27.3%, respectively). No associations were found between any of the pollutants or traffic indicators and carotid artery intima-media thickness, although PM2.5 effect estimates were in line with previous studies. We observed a 4.1% (95% confidence interval = 0.1% to 8.0%) increase in pulse wave velocity and a 37.6% (2.2% to 72.9%) increase in augmentation index associated with a 25 microg/m3 increase in NO2, and a 5.3% (0.1% to 10.4%) increase in pulse wave velocity with a 5 microg/m3 increase in SO2. PM2.5 and black smoke were not associated with either of these 2 outcomes.. Air pollution may accelerate arterial-wall stiffening in young adults. Small outcome variability and lack of residential mobility data may have limited the power to detect an effect on intima-media thickness.

Topics: Adult; Air Pollution; Arteriosclerosis; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Carotid Artery, Common; Environmental Exposure; Female; Humans; Linear Models; Male; Netherlands; Nitrogen Dioxide; Prospective Studies; Regression Analysis; Smoke; Sulfur Dioxide; Young Adult

Ambient exposure to nitrogen dioxide, a critical air pollutant in developed countries, is positively associated with cardiovascular mortality and morbidity. Although its cardiovascular effects are predominantly shown in patients with high risk of atherogenesis, no studies have elucidated whether daily exposure to nitrogen dioxide air pollution enhances atherogenic metabolisms, primarily in obese subjects who are susceptible to atherogenesis and subsequent cardiovascular diseases. We used male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as obese subjects and Long-Evans Tokushima (LETO) rats as nonobese controls. The animals were continuously exposed to nitrogen dioxide at a concentration of 0, 0.16, 0.8, or 4.0 ppm from 8 weeks of age through 32 weeks. At 40 weeks of age, levels of body weight, triglyceride, and total cholesterol were significantly greater in the OLETF rats than in the LETO rats. A ratio of high-density lipoprotein (HDL) to total cholesterol was significantly smaller in the former than in the latter. In the LETO rats, nitrogen dioxide exposure significantly decreased only the levels of HDL as compared with clean air exposure. In the OLETF rats, however, nitrogen dioxide exposure at a concentration of 0.16 ppm significantly elevated triglyceride concentration and decreased the ratio of HDL to total cholesterol as well as the levels of HDL. Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects.

Topics: Air Pollution; Animals; Arteriosclerosis; Blood Glucose; Body Weight; Cholesterol; Cholesterol, HDL; Humans; Inhalation Exposure; Male; Nitrogen Dioxide; Obesity; Oxidants, Photochemical; Rats; Rats, Long-Evans; Risk Factors; Triglycerides

Oxidized LDL is implicated in atherosclerosis; however, the pathways that convert LDL into an atherogenic form in vivo are not established. Production of reactive nitrogen species may be one important pathway, since LDL recovered from human atherosclerotic aorta is enriched in nitrotyrosine. We now report that reactive nitrogen species generated by the MPO-H2O2-NO2- system of monocytes convert LDL into a form (NO2-LDL) that is avidly taken up and degraded by macrophages, leading to massive cholesterol deposition and foam cell formation, essential steps in lesion development. Incubation of LDL with isolated MPO, an H2O2-generating system, and nitrite (NO2-)-- a major end-product of NO metabolism--resulted in nitration of apolipoprotein B 100 tyrosyl residues and initiation of LDL lipid peroxidation. The time course of LDL protein nitration and lipid peroxidation paralleled the acquisition of high-affinity, concentration-dependent, and saturable binding of NO2-LDL to human monocyte-derived macrophages and mouse peritoneal macrophages. LDL modification and conversion into a high-uptake form occurred in the absence of free metal ions, required NO2-, occurred at physiological levels of Cl-, and was inhibited by heme poisons, catalase, and BHT. Macrophage binding of NO2-LDL was specific and mediated by neither the LDL receptor nor the scavenger receptor class A type I. Exposure of macrophages to NO2-LDL promoted cholesteryl ester synthesis, intracellular cholesterol and cholesteryl ester accumulation, and foam cell formation. Collectively, these results identify MPO-generated reactive nitrogen species as a physiologically plausible pathway for converting LDL into an atherogenic form.

Topics: Animals; Arteriosclerosis; Cholesterol Esters; Humans; Hydrogen Peroxide; Lipid Peroxidation; Lipoproteins, LDL; Macrophages; Mice; Mice, Inbred C57BL; Monocytes; Nitrites; Nitrogen Dioxide; Peroxidase

Myeloperoxidase, a heme protein secreted by activated phagocytes, is present and enzymatically active in human atherosclerotic lesions. In the current studies, we explored the possibility that reactive nitrogen species generated by myeloperoxidase promote lipid peroxidation of low density lipoprotein (LDL) -- a modification that may render the lipoprotein atherogenic. We found that myeloperoxidase, an H2O2-generating system and nitrite (NO2-) peroxidized LDL lipids. The process required NO2- and each component of the enzymatic system; it was inhibited by catalase, cyanide and ascorbate, a potent scavenger of aqueous phase radicals. LDL peroxidation did not require chloride ion, and it was little affected by the hypochlorous acid scavenger taurine. Collectively, these results suggest that lipid peroxidation is promoted by a nitrogen dioxide radical-like species. These observations indicate that myeloperoxidase, by virtue of its ability to form reactive nitrogen intermediates, may promote lipid peroxidation and atherogenesis.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; Free Radicals; HL-60 Cells; Humans; Hydrogen Peroxide; Lipid Peroxidation; Lipoproteins, LDL; Nitrites; Nitrogen Dioxide; Peroxidase; Probucol; Vitamin E

Topics: Air Pollution; Animals; Arteriosclerosis; Carbon Monoxide; Cardiovascular Diseases; Cardiovascular System; Disease Models, Animal; Dogs; Electrocardiography; Female; Heart Rate; Hemodynamics; Hemoglobins; Hypertension; Methemoglobin; Myocardial Infarction; Nitric Oxide; Nitrogen Dioxide; Sulfoxides; Vectorcardiography; Vehicle Emissions