北京大學(xué)環(huán)境學(xué)院朱彤團(tuán)隊(duì)發(fā)現(xiàn)大氣污染影響動(dòng)脈粥樣硬化的潛在分子機(jī)制
大氣細(xì)顆粒物(PM2.5)在全球范圍內(nèi)每年造成約414萬人早逝,其中因動(dòng)脈粥樣硬化性心血管疾病早逝者占50%以上。然而,目前對(duì)PM2.5影響動(dòng)脈粥樣硬化性心血管疾病的分子機(jī)制的認(rèn)識(shí)還十分有限。鞘脂是一類脂質(zhì)生物調(diào)控分子,毒理學(xué)研究表明其通過影響機(jī)體內(nèi)含載脂蛋白B脂蛋白的水平促進(jìn)動(dòng)脈粥樣硬化風(fēng)險(xiǎn)。然而,在人群研究層面目前缺乏鞘脂在PM2.5影響動(dòng)脈粥樣硬化中作用的證據(jù)。
2013至2015年,北京大學(xué)環(huán)境科學(xué)與工程學(xué)院朱彤教授團(tuán)隊(duì)和北京大學(xué)醫(yī)院進(jìn)行合作,完成了對(duì)120名受試者共計(jì)589人次的健康隨訪。本研究基于團(tuán)隊(duì)自主研發(fā)的快速、高通量靶向鞘脂組學(xué)分析技術(shù),對(duì)受試者血漿中神經(jīng)酰胺、鞘磷脂、己糖神經(jīng)酰胺、乳糖神經(jīng)酰胺等多種鞘脂進(jìn)行了準(zhǔn)確定量測量,發(fā)現(xiàn)了大氣污染影響動(dòng)脈粥樣硬化的潛在分子機(jī)制。
研究發(fā)現(xiàn),PM2.5短期和中短期暴露可能促進(jìn)人體鞘脂合成(表現(xiàn)為側(cè)鏈含16至24個(gè)碳原子的神經(jīng)酰胺、鞘磷脂、己糖神經(jīng)酰胺和乳糖神經(jīng)酰胺水平的升高),其進(jìn)一步介導(dǎo)了體內(nèi)含載脂蛋白B脂蛋白水平的升高。該研究表明鞘脂可能是PM2.5影響動(dòng)脈粥樣硬化性心血管疾病的早期機(jī)制,提示基于鞘脂代謝的干預(yù)或許會(huì)降低空氣污染的心血管健康影響。
美國心臟協(xié)會(huì)心血管著名期刊Arteriosclerosis, Thrombosis, and Vascular Biology于2022年6月2日在線發(fā)表了朱彤團(tuán)隊(duì)的這一研究成果“Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids”。北京大學(xué)環(huán)境科學(xué)與工程學(xué)院的博士生徐一凡,以及現(xiàn)為英國帝國理工博士后的韓逸群為該論文共同第一作者,朱彤為通訊作者。該項(xiàng)研究獲得國家自然科學(xué)基金(21190051、91844000、41421064、41121004)和科技部“973”項(xiàng)目(2015CB553401)的支持,并獲得北京大學(xué)生物醫(yī)學(xué)倫理委員會(huì)的批準(zhǔn)(IRB0000105213024)。
論文信息及鏈接:
Xu Y, Han Y, Wang Y, et al. Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids. Arteriosclerosis, Thrombosis, and Vascular Biology, 2022; 42(7): 906-918.
SCOPE項(xiàng)目相關(guān)文章:
Xu Y, Li H, Han Y, et al. A simple and rapid method for extraction and measurement of circulating sphingolipids using LC–MS/MS: a targeted lipidomic analysis. Analytical and Bioanalytical Chemistry, 2022; 414(6): 2041-2054.
Chen W, Han Y, Wang Y, et al. Glucose metabolic disorders enhance vascular dysfunction triggered by particulate air pollution: A panel study. Hypertension, 2022;79(5):1079-1090.
Jiang X, Han Y, Qiu X, et al. Personal exposure to electrophilic compounds of fine particulate matter and the inflammatory response: The role of atmospheric transformation. Journal of Hazardous Materials. 2022;432:128559.
Lin Y, Zhang H, Han Y, et al. Field evaluation of a potential exposure biomarker of methylated polycyclic aromatic hydrocarbons: Association between urinary phenanthrene-2-carboxylic acid and personal exposure to 2-methylphenanthrene. Environmental Science & Technology Letters. 2022;9(2):166-172.
Wang T, Han Y, Li H, et al. Fine particulate matter and vasoactive 20-hydroxyeicosatetraenoic acid: Insights into the mechanisms of the prohypertensive effects of particulate air pollution. Science of The Total Environment. 2022;806(3):151298.
Shi Y, Han Y, Wang Y, et al. Serum branched-chain amino acids modifies the associations between air pollutants and insulin resistance. Ecotoxicology and Environmental Safety. 2021;225:112780.
Wang T, Han Y, Li H, et al. Proinflammatory lipid signals trigger the health effects of air pollution in individuals with prediabetes. Environmental Pollution, 2021;290:118008.
Jiang X, Han Y, Qiu X, et al. Organic components of personal PM2.5 exposure associated with inflammation: Evidence from an untargeted exposomic approach. Environmental Science & Technology. 2021;55(15):10589-10596.
Wang T, Han Y, Li H, et al. Changes in bioactive lipid mediators in response to short-term exposure to ambient air particulate matter: A targeted lipidomic analysis of oxylipin signaling pathways. Environmental International, 2021;147:106314.
Chen W, Han Y, Wang Y, et al. Associations between changes in adipokines and exposure to fine and ultrafine particulate matter in ambient air in Beijing residents with and without pre-diabetes. BMJ Open Diabetes Research and Care, 2020;8:e001215.
Fan Y, Han Y, Liu Y, et al. Biases arising from the use of ambient measurements to represent personal exposure in evaluating inflammatory responses to fine particulate matter: Evidence from a panel study in Beijing, China. Environmental Science & Technology Letters, 2020;7(10):746-752.
Chen X, Han Y, Chen W, et al. Respiratory inflammation and short-term ambient air pollution exposures in adult Beijing residents with and without prediabetes: A panel study. Environmental Health Perspectives, 2020;128(6):067004.
Zhang H, Han Y, Qiu X, et al. Association of internal exposure to polycyclic aromatic hydrocarbons with inflammation and oxidative stress in prediabetic and healthy individuals. Chemosphere, 2020;253:126748.
Han Y, Wang Y, Li W, et al. Susceptibility of prediabetes to the health effect of air pollution: a community-based panel study with a nested case-control design. Environmental Health, 2019;18:65.
Wang Y, Han Y, Zhu T, et al. A prospective study (SCOPE) comparing the cardiometabolic and respiratory effects of air pollution exposure on healthy and pre-diabetic individuals. Science China Life Science, 2018;61:46–56.
來源:北京大學(xué)


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