ABSTRACT
BACKGROUND: To investigate whether and what lifestyle factors in later life modify the associations of early-life smoking behaviors and genetic susceptibility with type 2 diabetes (T2D). METHODS: In the UK Biobank, in utero tobacco exposure (n = 354,493) and age of smoking initiation (n = 353,557) were self-reported. A composite lifestyle score was calculated based on diet, physical activity, nicotine exposure, sleep duration, and BMI. Hazard ratio (HR) and absolute risk difference (ARD) were used to estimate the associations of early-life smoking behaviors and genetic risk with incident T2D, as well as the effect modification of the lifestyle score. RESULTS: During a median follow-up of 14.6 years, the HRs (95 % CIs) of T2D for in utero tobacco exposure, and smoking initiation in adulthood, adolescence, and childhood, compared with no smoking behavior, were 1.19 (1.16-1.23), 1.34 (1.29-1.39), 1.58 (1.53-1.64), 2.22 (2.11-2.32), respectively (P for trend<0.001). Early-life smoking behaviors and high genetic risk (vs no smoking behavior and low genetic risk) were associated with a 302%-593 % higher T2D risk (P for additive interaction<0.05). Compared to participants with early-life smoking behaviors, high genetic risk, and an unfavorable lifestyle, those who adhered to a favorable lifestyle had a lower T2D risk in all subgroups (HRs from 0.05 to 0.36 and ARD from -14.97 % to -9.51 %), with the highest ARD attributable to lifestyle in participants with early-life smoking behaviors and high genetic risk. CONCLUSIONS: The T2D risk associated with early-life smoking behaviors and genetic risk was modified by a favorable lifestyle.
ABSTRACT
BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.
Subject(s)
Air Pollutants , Cardiovascular Diseases , Particulate Matter , Humans , Longitudinal Studies , China , Male , Adult , Young Adult , Female , Blood Pressure , Biomarkers/blood , Environmental Exposure/statistics & numerical data , Vascular Stiffness/drug effects , ProteomicsABSTRACT
OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear. RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models. RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07-1.27]) and CVD (HR, 1.09 [95% CI, 1.03-1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90-1.09]; HR for CVD, 1.04 [95% CI, 0.98-1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant. CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation.
Subject(s)
Cardiovascular Diseases , Cholesterol, Dietary , Humans , Male , Female , Cardiovascular Diseases/genetics , Cardiovascular Diseases/epidemiology , Middle Aged , Cholesterol, Dietary/adverse effects , Cholesterol, Dietary/administration & dosage , Diabetes Mellitus/genetics , Diabetes Mellitus/epidemiology , Aged , Adult , Genetic Predisposition to Disease , ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , Membrane Transport Proteins/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 5/geneticsABSTRACT
PURPOSE OF REVIEW: Air pollution has been a serious environmental and public health issue worldwide, particularly in Asian countries. There have been significant increases in epidemiological studies on fine particulate matter (PM2.5) and ozone pollution in East Asia, and an in-depth review of epidemiological evidence is urgent. Thus, we carried out a systematic review of the epidemiological research on PM2.5 and ozone pollution in East Asia released in recent years. RECENT FINDINGS: Recent studies have indicated that PM2.5 and ozone are the most detrimental air pollutants to human health, resulting in substantial disease burdens for Asian populations. Many epidemiological studies of PM2.5 and ozone have been mainly performed in three East Asian countries (China, Japan, and South Korea). We derived the following summary findings: (1) both short-term and long-term exposure to PM2.5 and ozone could raise the risks of mortality and morbidity, emphasizing the need for continuing improvements in air quality in East Asia; (2) the long-term associations between PM2.5 and mortality in East Asia are comparable to those observed in Europe and North America, whereas the short-term associations are relatively smaller in magnitude; and (3) further cohort and intervention studies are required to yield robust and precise evidence that can promote evidence-based policymaking in East Asia. This updated review presented an outline of the health impacts of PM2.5 and ozone in East Asia, which may be beneficial for the development of future regulatory policies and standards, as well as for designing subsequent investigations.
Subject(s)
Air Pollutants , Air Pollution , Environmental Exposure , Ozone , Particulate Matter , Humans , Air Pollution/adverse effects , Particulate Matter/analysis , Particulate Matter/adverse effects , Ozone/adverse effects , Ozone/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , Environmental Exposure/adverse effects , Asia, Eastern , Public HealthABSTRACT
BACKGROUND: Few large-scale, nationwide studies have assessed cause-specific mortality risks and burdens associated with temperature variability (TV). OBJECTIVE: To estimate associations between TV and cause-specific mortality and quantify the mortality burden in China. METHODS: Data on daily total and cause-specific mortality in 272 Chinese cities between 2013 and 2015 were recorded. TVs were computed as the standard deviations of daily minimum and maximum temperatures over a duration of 2 to 7 days. The time-series quasi-Poisson regression model with adjustment of the cumulative effects of daily mean temperature over the same duration was applied to evaluate the city-specific associations of TV and mortality. Then, we pooled the effect estimates using a random-effects meta-analysis and calculated the mortality burdens. RESULTS: Overall, TV showed significant and positive associations with total and cause-specific mortality. The TV-mortality associations were generally stronger when using longer durations. A 1 °C increase in TV at 0-7 days (TV0-7) was associated with a 0.79 % [95 % confidence interval (CI): 0.55 %, 0.96 %] increase in total mortality. Mortality fractions attributable to TV0-7 were 4.37 % for total causes, 4.75 % for overall cardiovascular disease, 4.37 % for coronary heart disease, 5.05 % for stroke, 8.28 % for ischaemic stroke, 1.08 % for haemorrhagic stroke, 6.93 % for respiratory disease, and 6.81 % for COPD, respectively. The mortality risk and burden were generally higher in the temperate monsoon zone, females, and elders. CONCLUSION: This nationwide study indicated that TV was an independent risk factor of mortality, and could result in significant burden for main cardiorespiratory diseases.
Subject(s)
Brain Ischemia , Stroke , Aged , Female , Humans , Cause of Death , China/epidemiology , Cities/epidemiology , Cold Temperature , Environmental Exposure , Hot Temperature , Mortality , Temperature , MaleABSTRACT
BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.
Subject(s)
Air Pollutants , Air Pollution , Adult , Humans , Air Pollutants/toxicity , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Environmental Exposure/analysis , Pulmonary Surfactant-Associated Protein D/analysis , Pulmonary Surfactant-Associated Protein D/metabolism , Particulate Matter/toxicity , Particulate Matter/analysis , Vehicle Emissions/toxicity , Vehicle Emissions/analysis , Biomarkers/analysis , Metabolome , LungABSTRACT
Changes in human genome-wide long noncoding RNAs (lncRNAs) associated with air pollution are unknown. This study aimed to investigate the effect of air pollution on human exosomal lncRNAs. A randomized, crossover trial was conducted among 35 healthy adults. Participants were allocated to 4 h exposure in road (high air pollution) and park (low air pollution) sessions in random order with a 2 week washout period. RNA sequencing was performed to measure lncRNAs. Differential lncRNAs were identified using a linear mixed-effect model. Mean concentrations of air pollutants such as ultrafine particles (UFP), black carbon (BC), carbon monoxide (CO), and nitrogen dioxide (NO2) were 2-3 times higher in the road than those in the park. Fifty-five lncRNAs [false discovery rate (FDR) < 0.05] including lncRNA NORAD, MALAT1, and H19 were changed in response to air pollution exposure. We found that 54 lncRNAs were associated with CO, 49 lncRNAs with UFP, 49 lncRNAs with BC, 48 lncRNAs with NO2, and 4 lncRNAs with PM2.5 (FDR < 0.05). These differential lncRNAs participated in dozens of pathways including cardiovascular signaling, epithelial cell proliferation, inflammation, and transforming growth factor. This trial for the first time profiled changes of human exosomal lncRNAs following air pollution. Our findings revealed multiple biological processes moderated by lncRNAs and provided epigenetic insights into cardiovascular effects of air pollution.
Subject(s)
Air Pollutants , Air Pollution , RNA, Long Noncoding , Adult , Humans , RNA, Long Noncoding/genetics , Nitrogen Dioxide/analysis , Environmental Exposure/analysis , Cross-Over Studies , Air Pollution/analysis , Air Pollutants/analysis , Particulate Matter/analysisABSTRACT
BACKGROUND: Traffic-related air pollution (TRAP) has been associated with changes in gene-specific DNA methylation. However, few studies have investigated impact of TRAP exposure on genome-wide DNA methylation in circulating blood of human. OBJECTIVE: To explore the association between TRAP exposure and genome-wide DNA methylation. METHODS: We conducted a randomized, crossover exposure trial among 35 healthy adults in Shanghai, China. All subjects were randomly allocated to a traffic-free park or a main road for consecutive 4 h, respectively. Blood genome-wide DNA methylation after each exposure session was measured by the Infinium Methylation EPIC BeadChip (850K). The differentially methylated CpGs loci associated with TRAP exposure were identified using linear mixed-effect model. RESULTS: The average concentrations of traffic-related air pollutants including black carbon, ultrafine particles, carbon dioxide, and nitrogen dioxide were 2-3 times higher in the road compared to those in the park. Methylation levels of 68 CpG loci were significantly changed (false discovery rate < 0.05) following TRAP exposure, among which 49 were hypermethylated and 19 were hypomethylated. The annotated genes based on the differential CpGs loci were related to pathways in cardiovascular signaling, cytokine signaling, immune response, nervous system signaling, and metabolism. CONCLUSIONS: We found that TRAP exposure was associated with DNA methylation in dozens of genes concerning cardiometabolic health. This trial for the first-time profiled genome-wide methylation changes induced by TRAP exposure using the 850K assay, providing epigenetic insights in understanding the cardiometabolic effects of TRAP exposure.
Subject(s)
Air Pollutants , Air Pollution , Cardiovascular Diseases , Adult , Air Pollutants/analysis , Air Pollution/analysis , Carbon Dioxide , China , Cross-Over Studies , Cytokines/genetics , DNA , DNA Methylation , Environmental Exposure/analysis , Humans , Nitrogen Dioxide/analysis , Particulate Matter/analysis , Vehicle EmissionsABSTRACT
BACKGROUND: The underlying mechanisms for health effects of traffic-related air pollution (TRAP) are still unclear. Small RNA sequencing (RNA-seq) in exosomes represents as a powerful approach to elucidate biological pathways in response to environmental exposure. We therefore aimed to explore impact of TRAP exposure on exosomal miRNAs. METHODS: We performed a randomized, crossover study among 35 healthy college students in Shanghai, China. Participants were randomly assigned to 4-hour exposure in a traffic-polluted Road and in a traffic-free Park, respectively, intermitted by a washout period (at least 2 weeks). RNA-seq was conducted to identify plasma-derived exosomal miRNAs and the differential miRNAs were explored using linear mixed-effect models. Pathway enrichment was conducted using ingenuity pathway analysis. Further, we validated several selected miRNAs by droplet digital PCR (ddPCR). RESULTS: The average concentrations of air pollutants including ultrafine particles, black carbon, nitrogen dioxide, and carbon dioxide were 2-3 times higher in the Road compared to those in the Park. We identified 271 exosomal miRNAs (212 up-regulated and 59 down-regulated) that were significantly associated with TRAP. We found 5 miRNAs with 242 experimentally validated mRNA targets that were involved in cardiovascular pathway, cytokine signaling, and immune response. The ddPCR analysis suggested that miR-3612, miR-21-5p, and miR-195-5p were significantly changed following TRAP exposure. CONCLUSIONS: For the first time this trial characterized the genome-wide changes of exosomal miRNA associated with TRAP exposure. The molecular profiling of exosomal miRNAs and "novel" associations of some miRNAs were useful for understanding on biological mechanisms for the adverse effects of TRAP.
Subject(s)
Air Pollution , MicroRNAs , China , Cross-Over Studies , Humans , MicroRNAs/genetics , Sequence Analysis, RNAABSTRACT
A system-wide cardiovascular response to traffic-related air pollution (TRAP) has been rarely described. To systemically understand the mechanisms underlying cardiovascular effects of TRAP, we conducted a randomized, crossover trial in 56 young adults, who engaged in two 4-hour exposure sessions on a main road and in a park, alternately. We measured personal exposures to traffic-related air pollutants (TRAPs), including fine and ultrafine particulate matter, black carbon, nitrogen dioxide, and carbon monoxide. Lipidomics, targeted proteomics, urine metabolomics, targeted biomarkers, ambulatory blood pressure and electrocardiogram were measured. We used linear mixed-effects models to estimate the associations. The exposures to TRAPs except for fine particulate matter in the road session were 2-3 times higher. We observed elevated blood pressure and decreased heart rate variability (HRV) after TRAP exposure, accompanied by dozens of molecular alterations involving systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and lipid metabolism. Pathways like vascular smooth muscle cell proliferation and biomarkers like trimethylamine N-Oxide might also be disturbed. Some of these TRAP-related molecular biomarkers were also associated with changes of blood pressure or HRV. Our results provided systematical mechanistic profiling for the cardiovascular effects of TRAP using multi omics, which may have implications in TRAP control.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Biomarkers/analysis , Blood Pressure Monitoring, Ambulatory , Cross-Over Studies , Environmental Exposure/analysis , Humans , Particulate Matter/analysis , Particulate Matter/toxicity , Vehicle Emissions/analysis , Vehicle Emissions/toxicity , Young AdultABSTRACT
RATIONALE: Transcriptome-wide analysis is powerful in studying systemic RNA changes following environmental exposures. However, impacts of ozone inhalation on circulating transcriptome have not yet been examined. OBJECTIVES: To explore the impact of acute ozone exposure on circulating transcriptome using RNA sequencing (RNA-seq). METHODS: We recruited 32 healthy young adults in a randomized, crossover, controlled exposure trial. Each participant completed two 2-h exposure sessions of ozone (200 ppb) and clean air, respectively. Blood samples were collected at the end of each session and were used for RNA-seq. The differentially expressed genes associated with ozone exposure were assessed using Bayesian adjusted statistics from linear models in the limma R package. RESULTS: A total of 29 participants finished this trial and donated their blood samples for transcriptome analysis. The average concentration of ozone was 7.8 ± 2.6 ppb under clean air and 201.1 ± 1.7 ppb under ozone exposure session. A total of 1899 genes were significantly changed (1067 up-regulated and 832 down-regulated) by ozone exposure at a false discovery rate < 0.05, in which 403 genes had a fold change of > 1.2 or < 0.8. The top 10 terms of biological processes showed that most of the differentially expressed genes were related to various functions, such as neutrophil degranulation, immune response, and neutrophil activation. Pathway enrichment analysis showed dozens of pathways were dysregulated after ozone exposure, including mitochondrial dysfunction, and glucocorticoid receptor signaling. CONCLUSION: For the first time this trial characterized the genome-wide changes of mRNA in response to ozone exposure. We identified a range of differentially expressed genes that were involved in dozens of biological processes and pathways, providing novel biological insights into the systemic health effects of ozone.
Subject(s)
Air Pollutants , Ozone , Air Pollutants/toxicity , Bayes Theorem , Cross-Over Studies , Humans , Ozone/toxicity , Transcriptome , Young AdultABSTRACT
Epidemiological studies have associated ozone exposure with cardiovascular diseases, but the molecular mechanisms were not elucidated. We performed an untargeted serum proteomic analysis in a randomized, crossover, controlled exposure trial. We recruited 32 healthy young adults and asked them to receive filtered air and 200-ppb ozone exposures for 2 h in a random order before serum collection. Linear mixed-effect models were used to identify differentially expressed proteins (DEPs) between the two exposures and Gene Ontology enrichment and ingenuity pathway analysis were performed to determine their biological function. A total of 56 DEPs were identified. For example, acute ozone exposure increased coagulation factor X and factor VII-activating protease by 20.96% and 28.35%, respectively. Whereas, protein Z, protein Z-dependent protease inhibitor, and plasminogen decreased by 13.62%, 33.54%, and 10.47%, respectively. We also observed a 42.32% decrease in paraoxonase 3 and evident changes in four apolipoproteins. Additionally, we found 18.21% and 95.82% increases in L-selectin and ß2-microglobulin, respectively, and significant changes in three complements. DEPs and enriched pathways suggest that short-term ozone exposure may promote coagulation, suppress fibrinolysis, disrupt lipoprotein metabolism, activate immune responses, and affect the complement system. These findings provide additional insights into the mechanisms linking acute ozone exposure to thrombosis.
Subject(s)
Air Pollutants , Ozone , Air Pollutants/toxicity , Blood Coagulation , Cross-Over Studies , Humans , Ozone/toxicity , Proteomics , Young AdultABSTRACT
The biological mechanism of adverse health outcomes related to exposure to traffic-related air pollution (TRAP) needs elucidation. We conducted a randomized, crossover trial among healthy young students in Shanghai, China. Participants wore earplugs and were randomly assigned to a 4-hour walking treatment either along a traffic-polluted road or through a traffic-free park. We conducted untargeted analyses of plasma exosome transcriptomics, serum mass spectrometry-based proteomics, and serum metabolomics to evaluate changes in genome-wide transcription, protein, and metabolite profiles in 35 randomly selected participants. Mean personal exposure levels of ultrafine particles, black carbon, nitrogen dioxide, and carbon monoxide in the road were 2-3 times higher than that in the park. We observed 3449 exosome mRNAs, 58 serum proteins, and 128 serum metabolites that were significantly associated with TRAP. The multi-omics analysis showed dozens of regulatory pathways altered in response to TRAP, such as inflammation, oxidative stress, coagulation, endothelin-1 signaling, and renin-angiotensin signaling. We found that several novel pathways activated in response to TRAP exposure: growth hormone signaling, adrenomedullin signaling, and arachidonic acid metabolism. Our study served as a demonstration and proof of concept on the evidence that associated TRAP exposure with global molecular changes based on the multi-omics level.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , China , Cross-Over Studies , Environmental Exposure/analysis , Humans , Particulate Matter/analysis , Particulate Matter/toxicityABSTRACT
The biological mechanisms underlying the associations between atmospheric ozone exposure and adverse cardiometabolic outcomes are yet to be identified. Imbalanced autonomic nervous system (ANS) as well as activations of the sympatho-adrenomedullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axes are among possible early biological responses triggered by ozone, and may eventually lead to cardiometabolic abnormalities. To determine whether acute ozone exposure causes ANS imbalance and increases the secretion of neuroendocrine stress hormones, we conducted a randomized, double-blind, crossover trial, under controlled 2-hour exposure to either ozone (200 ppb) or clean air with intermittent exercise among 22 healthy young adults. Here we found that, compared to clean air exposure, acute ozone exposure significantly decreased the high-frequency band of heart rate variability, even after adjusting for heart rate and pre-exposure to ambient air pollutants and meteorological factors. Ozone exposure also significantly increased the serum levels of stress hormones, including corticotrophin-releasing factor, adrenocorticotropic hormone, adrenaline, and noradrenaline. Metabolomics analysis showed that acute ozone exposure led to alterations in stress hormones, systemic inflammation, oxidative stress, and energy metabolism. Our results suggest that acute ozone exposure may trigger ANS imbalance and activate the HPA and SAM axes, offering potential biological explanations for the adverse cardiometabolic effects following acute ozone exposure.
Subject(s)
Air Pollutants , Ozone , Cross-Over Studies , Heart Rate , Hormones , Humans , Ozone/toxicity , Young AdultABSTRACT
PM2.5-related neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. Six-week-old male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM2.5 or filtered air for 2, 4, and 6 months, respectively. The neurobehavioral changes of mice were tested. The weight of the whole brain and olfactory bulbs were recorded at the end of exposure, and the brain structure was observed by hematoxylin and eosin (HE) staining. Serum indicators, mRNA, and protein expressions were detected. The spatial learning memory ability was impaired, and the mice were more anxious after PM2.5 exposure. Relative brain weight decreased with age, and PM2.5 exposure exceeded the decrease of relative brain weight. Interestingly, superoxide dismutase (SOD) and albumin decreased in the PM2.5-exposed groups although neuronal morphology and other serum indicators did not show significant difference between PM and FA groups. Moreover, PM2.5 induced the increase of plasminogen at 2 months but recovered at 4 months and then increased at 6 months again. The results from protein expression and transcriptomic test demonstrated that PI3K/AKT/FoxO1 pathway might be activated after 6-month PM2.5 exposure in mice. Indicators albumin, the percentage of albumin over IgG (A/G value), and plasminogen were the main serous changes in mice after early-stage (2 months) and long-term (6 months) PM2.5 exposure. In addition, early-stage injury induced by PM2.5 might recover at later time point and display significant injury again with the exposure time. PM2.5 exposure-induced brain injury might be associated with the activation of PI3K/AKT/FoxO1 pathway.
Subject(s)
Air Pollutants , Brain Injuries , Air Pollutants/analysis , Animals , Forkhead Box Protein O1/metabolism , Male , Mice , Mice, Inbred C57BL , Oxidative Stress , Particulate Matter/analysis , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Epidemiological evidences have indicated that fine particulate matter (PM2.5 ) exposure is associated with the occurrence and development of hypertension. The present study aims to explore the effects of parental PM2.5 exposure on blood pressure in offspring and elucidate the potential mechanism. The parental male and female C57BL/6 mice were exposed to concentrated PM2.5 or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 16 weeks. At week 12, the mice were assigned to breed offspring. The male offspring mice were further exposed to PM2.5 or FA as above method. During the parental exposure, the average PM2.5 concentration was 133.7 ± 53.32 µg/m3 in PM chamber, whereas the average concentration in FA chamber was 9.4 ± 0.23 µg/m3 . Similarly, during the offspring exposure, the average concentration in PM and FA chamber were 100.76 ± 26.97 µg/m3 and 9.15 ± 0.15 µg/m3 , respectively. The PM2.5 -exposed offspring mice displayed the elevation of blood pressure, the increase of angiotensin II (Ang II), the decrease of angiotensin converting enzyme 2 (ACE2) and Ang (1-7) in serum when compared with the FA-exposed offspring mice. The similar results displayed in the proteins expression of ACE2, AT1R, and Ang (1-7) in vessel and kidney. More importantly, parental PM exposure further induced the increase in serous Ang II and the protein expression of AT1R in vessel, but decrease in ACE2 and Ang (1-7). The serous Ang II was positively associated with splenic T helper type 17 (Th17) cell population and serous IL (interleukin)-17A, but negatively associated with T regular (Treg) cell population and serous IL-10. The results suggested that parental air pollution exposure might induce the elevation of offspring blood pressure via mediate Th17- and Treg-related immune microenvironment.
Subject(s)
Particulate Matter , T-Lymphocytes, Regulatory , Animals , Blood Pressure , China , Female , Male , Mice , Mice, Inbred C57BL , Particulate Matter/toxicityABSTRACT
BACKGROUND: Limited evidence is available on the associations of long-term exposure to various fine particulate matter (PM2.5) constituents with sub-clinical outcomes of cardiovascular disease (CVD) in China. OBJECTIVES: We aimed to explore the associations of PM2.5 and its constituents with blood pressure (BP), fasting glucose, and cardiac electrophysiological (ECG) properties based on a national survey of 5852 Chinese adults, who participated in the Sub-Clinical Outcome of Polluted Air study, from July 2017 to March 2019. METHODS: Annual residential exposure to PM2.5 and its constituents of each subject was predicted by a satellite-based mode. We assessed the associations between five main constituents [organic matter (OM), black carbon (BC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+)] of PM2.5 and systolic BP (SBP), diastolic BP (DBP), fasting glucose, and ECG measurements (PR, QRS, QT, and QTc interval) using multivariable linear regression models. RESULTS: Long-term PM2.5 exposure was significantly associated with increased levels of fasting glucose, DBP, and ECG measurements. An IQR increase in OM (8.2 µg/m3) showed considerably stronger associations with an elevated fasting glucose of 0.39 mmol/L (95%CI confidence interval: 0.28, 0.49) compared with other PM2.5 constituents. Meanwhile, an IQR increase in NO3-, NH4+ and OM had stronger associations with DBP and ECG parameters compared with BC and SO42-. CONCLUSIONS: This nationwide multi-center study in China indicated that some constituents (i.e., OM, NO3-, and NH4+) might be mainly responsible for the association of PM2.5 with sub-clinical outcomes of CVD including BP, fasting glucose, and ECG measurements.
Subject(s)
Air Pollutants , Air Pollution , Cardiovascular Diseases , Adult , Air Pollutants/analysis , Air Pollution/analysis , Cardiovascular Diseases/epidemiology , China/epidemiology , Environmental Exposure/analysis , Humans , Particulate Matter/adverse effects , Particulate Matter/analysisABSTRACT
BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.
Subject(s)
Air Pollutants/toxicity , Angiotensin I/metabolism , Blood Pressure/drug effects , Hypertension/chemically induced , Particulate Matter/toxicity , Peptide Fragments/metabolism , Peptidyl-Dipeptidase A/metabolism , Acetylglucosaminidase/urine , Angiotensin I/blood , Angiotensin-Converting Enzyme 2 , Animals , Biomarkers/blood , Biomarkers/urine , Hypertension/urine , Lipid Metabolism/drug effects , Male , Metabolome/drug effects , Metabolomics , Mice , Mice, Inbred C57BL , Peptide Fragments/blood , Peptidyl-Dipeptidase A/blood , Renin-Angiotensin System/drug effects , beta-Galactosidase/urineABSTRACT
Both the epidemiological and animal experimental studies have reported the association between PM2.5 and respiratory, cardiovascular, and metabolic diseases. However, the study linking PM2.5 and hepatic injury is few, and the relative mechanism has not been fully elucidated. Thirty-two 6-week-old male C57BL/6 mice were exposed to filtered air (FA) or concentrated PM2.5 for 12 weeks using Shanghai Meteorological and Environmental Animal Exposure System ("Shanghai-METAS"), respectively. At week 11, the mice began to be treated with intraperitoneal injection of normal 0.9% saline or AMPK activator (AICAR). The mRNA levels of IL-6 and TNF-α, and protein expressions of AMPK, GLUT4, NF-κB, p38MAPK, ERK, and JNK in the liver and UCP-1 in brown adipose tissue (BAT) were measured. Meanwhile, histopathological examination both in the liver and BAT was performed to evaluate the histopathological changes. PM2.5 exposure induced steatosis, hepatocyte ballooning, lobular and portal inflammation in the liver, and the brown adipocyte swelling in BAT. The results found that PM mice displayed higher IL-6, TNF-α, NF-κB, and JNK expression and lower AMPK, GLUT4, and UCP-1 when compared with FA mice. The AICAR injection upregulated the expressions of GLUT4 in the liver of PM-AIC mice when compared with the PM mice. However, there were no significant effects of AICAR on histopathological condition. The current study showed that ambient PM2.5 exposure might induce the hepatic injury along with the lipid metabolism disorder in BAT. AMPK activation can ameliorate most of the harmful effects and might become the potential target for treating PM2.5-induced hepatic injury.
Subject(s)
Air Pollutants , Particulate Matter , AMP-Activated Protein Kinases , Animals , China , Liver , Male , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: A new Air Quality Health Index (AQHI) was developed in Canada or several single cities as a promising health risk communication tool. OBJECTIVES: To construct a national AQHI in China and compare its validity in predicting daily mortality risk with the existing Air Quality Index (AQI). METHODS: We established the AQHI as the sum of excess total mortality risks associated with multiple air pollutants in 272 representative Chinese cities from 2013 to 2015 (termed as "total AQHI"). The mortality risks per unit change of air pollutant concentrations were determined according to a time-series analysis in each city. Separate AQHIs were established for subgroups classified by age and sex and for main cardiopulmonary diseases (termed as "specific AQHIs"). For validation, AQHIs and AQI were established using the data of 2015 (N = 272) and compared their associations with daily mortality using the data of 2013-2014 (N = 144). RESULTS: The concentration-response coefficients of fine particulate matter, nitrogen dioxide and ozone were adopted in constructing AQHI. There were almost linear exposure-response relationships between AQHIs and daily mortality. The total AQHI and specific AQHIs had very similar associations with daily mortality. AQHI and AQI showed similar associations with daily cause-specific mortality in terms of average magnitude, numbers of cities of positive associations and model fit statistics. CONCLUSIONS: AQHI may have comparable performance with AQI in communicating acute health risks of air pollution in China. There seems no need to establish specific AQHIs for different age groups, gender and causes of deaths.