Lixian Sun

Air pollution-mediated susceptibility to inflammation and insulin resistance: Influence of CCR2 pathways in mice

Background: Epidemiologic and experimental studies support an association between PM2.5 exposure and insulin resistance (IR). Innate immune cell activation has been suggested to play a role in the pathogenesis of these effects. Objectives: We sought to evaluate the role of CC-chemokine receptor 2 (CCR2) in PM2.5-mediated inflammation and IR. Methods: Wild-type C57BL/6 and CCR2–/– male mice were fed a high-fat diet and exposed to either concentrated ambient PM2.5 or filtered air for 17 weeks via a whole-body exposure system. We evaluated glucose tolerance and insulin sensitivity. At euthanasia, blood, spleen, and visceral adipose tissue (VAT) were collected, and inflammatory cells were measured using flow cytometry. We used standard immunoblots, immunohistochemical methods, and quantitative PCR (polymerase chain reaction) to assess pathways of interest involving insulin signaling, inflammation, and lipid and glucose metabolism in various organs. Vascular function was assessed using myography. Results: PM2.5 exposure resulted in whole-body IR and increased hepatic lipid accumulation in the liver, which was attenuated in CCR2–/– mice by inhibiting SREBP1c-mediated transcriptional programming, decreasing fatty acid uptake, and suppressing p38 MAPK activity. Abnormal phosphorylation levels of AKT, AMPK in VAT, and adipose tissue macrophage content in wild-type mice were not present in CCR2–/– mice. However, the impaired whole-body glucose tolerance and reduced GLUT-4 in skeletal muscle in response to PM2.5 was not corrected by CCR2 deficiency. Conclusions: PM2.5 mediates IR by regulating VAT inflammation, hepatic lipid metabolism, and glucose utilization in skeletal muscle via both CCR2-dependent and -independent pathways. These findings provide new mechanistic links between air pollution and metabolic abnormalities underlying IR. Citation: Liu C, Xu X, Bai Y, Wang TY, Rao X, Wang A, Sun L, Ying Z, Gushchina L, Maiseyeu A, Morishita M, Sun Q, Harkema JR, Rajagopalan S. 2014. Air pollution–mediated susceptibility to inflammation and insulin resistance: influence of CCR2 pathways in mice. Environ Health Perspect 122:17–26; http://dx.doi.org/10.1289/ehp.1306841

Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study

Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m3 and 0.2 to 24.5 µg/m3, respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3–3.7) to 2.7 (0.6–4.8) mm Hg per SD increase (67.2 µg/m3), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0–2.5) to 1.7 (0.3–3.2) mm Hg per SD increase (3.6 µg/m3). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01–0.36] and 0.22 [0.04–0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02–0.34] and 0.22 [0.08–0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

Personal Black Carbon Exposure Influences Ambulatory Blood Pressure Air Pollution and Cardiometabolic Disease (AIRCMD-China) Study

Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) μg/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution. # Novelty and Significance {#article-title-34}Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) &mgr;g/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.

Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin ResistanceNovelty and Significance

Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m3 and 0.2 to 24.5 µg/m3, respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3–3.7) to 2.7 (0.6–4.8) mm Hg per SD increase (67.2 µg/m3), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0–2.5) to 1.7 (0.3–3.2) mm Hg per SD increase (3.6 µg/m3). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01–0.36] and 0.22 [0.04–0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02–0.34] and 0.22 [0.08–0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

Personal Black Carbon Exposure Influences Ambulatory Blood Pressure

Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) μg/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution. # Novelty and Significance {#article-title-34}Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) &mgr;g/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.

Personal Black Carbon Exposure Influences Ambulatory Blood PressureNovelty and Significance

Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) μg/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution. # Novelty and Significance {#article-title-34}Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) &mgr;g/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.

Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin ResistanceNovelty and Significance: The Air Pollution and Cardiometabolic Disease Study

Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m3 and 0.2 to 24.5 µg/m3, respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3–3.7) to 2.7 (0.6–4.8) mm Hg per SD increase (67.2 µg/m3), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0–2.5) to 1.7 (0.3–3.2) mm Hg per SD increase (3.6 µg/m3). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01–0.36] and 0.22 [0.04–0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02–0.34] and 0.22 [0.08–0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance

Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m3 and 0.2 to 24.5 µg/m3, respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3–3.7) to 2.7 (0.6–4.8) mm Hg per SD increase (67.2 µg/m3), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0–2.5) to 1.7 (0.3–3.2) mm Hg per SD increase (3.6 µg/m3). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01–0.36] and 0.22 [0.04–0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02–0.34] and 0.22 [0.08–0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

Personal Black Carbon Exposure Influences Ambulatory Blood PressureNovelty and Significance: Air Pollution and Cardiometabolic Disease (AIRCMD-China) Study

Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) μg/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution. # Novelty and Significance {#article-title-34}Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia’s megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four–hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) &mgr;g/m3. Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17–0.89 and 0.10–0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of −0.06 (95% confidence interval, 0.62–9.60 and −0.11 to −0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.