肥胖儿童脂肪组织内质网应激促动脉粥样硬化研究进展
王明夏 贾丽红 翟玲玲 魏薇 孙琦 白英龙
中国医科大学公共卫生学院儿少卫生与妇幼保健学教研室,辽宁沈阳 110122
Research progress on atherosclerosis promoted by endoplasmic reticulum stress of adipose tissue in children with obesity
WANG Mingxia JIA Lihong ZHAI Lingling WEI Wei SUN Qi BAI Yinglong
Department of Child and Adolescent Health, School of Public Health, China Medical University, Liaoning Province, Shenyang 110122, China
摘要 心血管疾病是当前威胁我国人民健康最严重的公共卫生问题。动脉粥样硬化是其主要病理基础,可发生于儿童时期,肥胖儿童患病风险增高。内质网应激是动脉粥样硬化发生发展的重要机制。肥胖的脂肪组织中巨噬细胞浸润增多,内质网应激加剧,脂肪细胞与巨噬细胞间交互作用也加速动脉粥样硬化进程,在动脉粥样硬化性心血管疾病的发生发展中起重要作用。本文就脂肪组织内质网应激与肥胖儿童动脉粥样硬化发生发展关系的相关机制进行综述,旨在加深人们对肥胖加速儿童患动脉粥样硬化疾病的理解,提高人们预防儿童肥胖的认识,并为肥胖引发的儿童动脉粥样硬化的治疗开拓新思路。
关键词 :
儿童肥胖 ,
脂肪组织 ,
内质网应激 ,
动脉粥样硬化 ,
心血管疾病
Abstract :Cardiovascular disease is the most serious public health problem that currently threatens the health of people in our country. Atherosclerosis is the main pathological basis and can occur in childhood, and the risk of obesity in children is increasing. Endoplasmic reticulum stress is an important mechanism for the development of atherosclerosis. Macrophage infiltration in obese adipose tissue increases, endoplasmic reticulum stress aggravates, interaction between adipocytes and macrophages accelerates atherosclerotic progression, which plays an important role in the development of atherosclerotic cardiovascular disease. For deepening people′s knowledge of obesity accelerating atherosclerosis and raising awareness of preventing childhood obesity, and exploiting new ideas for treating atherosclerosis in children with obesity, this review introduced the relationship between endoplasmic reticulum stress of adipose tissue and the development of atherosclerosis in children with obesity.
Key words :
Childhood obesity
Adipose tissue
Endoplasmic reticulum stress
Atherosclerosis
Cardiovascular disease
基金资助: 国家自然科学基金资助项目(81373018,81172691)。
通讯作者:
白英龙(1976.4-),女,博士,副教授,硕士生导师;研究方向:儿童肥胖。
作者简介 : 王明夏(1991.8-),女,中国医科大学公共卫生学院2016级公共卫生专业在读硕士研究生;研究方向:儿童肥胖。
[1] Clarke R,Du H,Kurmi O,et al. Burden of carotid artery atherosclerosis in Chinese adults:Implications for future risk of cardiovascular diseases [J]. Eur J Prev Cardiol,2017, 24(6):647-656.
[2] Mendizabal B,Urbina EM. Subclinical atherosclerosis in youth:relation to obesity,insulin resistance,and polycystic ovary syndrome [J]. J Pediatr,2017,190:14-20.
[3] WHO. Obesity[EB/OL].(2017-10)[2018-5-30]. http://www.who.int/topics/obesity/en/.
[4] Yan Y,Hou D,Liu J,et al. Effect of childhood adiposity on long-term risks of carotid atherosclerosis and arterial stiffness in adulthood [J]. Zhonghua Yu Fang Yi Xue Za Zhi,2016,50(1):28-33.
[5] Olson M,Chambers M,Shaibi G. Pediatric markers of adult cardiovasculardisease [J]. Curr Pediatr Rev,2017,13(4):255-259.
[6] Nuotio J,Pitkanen N,Magnussen CG,et al. Prediction of adult dyslipidemia using genetic and childhood clinical risk factors:the cardiovascular risk in young finns study [J]. Circ Cardiovasc Genet,2017,10(3):pii:e001604.
[7] Unal E,Akin A,Yildirim R,et al. Association of subclinical hypothyroidism with dyslipidemia and increased carotid intima-media thickness in children [J]. J Clin Res Pediatr Endocrinol,2017,9(2):144-149.
[8] Wendell CR,Waldstein SR,Evans MK,et al. Distributions of subclinical cardiovascular disease in a socioeconomically and racially diverse sample [J]. Stroke,2017,48(4):850-856.
[9] Li S,Chen W,Srinivasan SR,et al. Childhood cardiovascular risk factorsand carotid vascular changes in adulthood:the bogalusa heart study [J]. JAMA,2003,290(17):2271-2276.
[10] Choy KW,Murugan D,Mustafa MR. Natural products targeting ER stresspathway for the treatment of cardiovascular diseases [J]. Pharmacol Res,2018,132:119-129.
[11] Saksi J,Ijas P,Mayranpaa MI,et al. Low-expression variant of fatty acid-binding protein 4 favors reduced manifestations of atherosclerotic disease and increased plaque stability [J]. Circ Cardiovasc Genet,2014,7(5):588-598.
[12] Rabar S,Harker M,O′Flynn N,et al. Lipid modification and cardiovascular risk assessment for the primary and secondary prevention of cardiovascular disease:summary of updated NICE guidance [J]. BMJ,2014,349:g4356.
[13] Dickhout JG,Lhotak S,Hilditch BA,et al. Induction of the unfolded protein response after monocyte to macrophage differentiation augments cell survival in early atherosclerotic lesions [J]. FASEB J,2011,25(2):576-589.
[14] Go AS,Mozaffarian D,Roger VL,et al. Executive summary:heart disease and stroke statistics--2013 update:a report from the American Heart Association[J]. Circulation,2013,127(1):143-152.
[15] Kang PP,Yao ST,Guo TT,et al. Activating transcription factor 6-C/EBP homologous protein pathway mediates advanced glycated albumin-induced macrophage apoptosis [J]. Sheng Li Xue Bao,2017,69(6):767-774.
[16] Sun J,Cui J,He Q,et al. Proinsulin misfolding and endoplasmic reticulum stress during the development and progression of diabetes [J]. Mol Aspects Med,2015,42:105-118.
[17] Wakana N,Irie D,Kikai M,et al. Maternal high-fat diet exaggerates atherosclerosis in adult offspring by augmenting periaortic adipose tissue-specific proinflammatory response [J]. Arterioscler Thromb Vasc Biol,2015,35(3):558-569.
[18] Weisberg SP,McCann D,Desai M,et al. Obesity is associated with macrophage accumulation in adipose tissue [J]. J Clin Invest,2003,112(12):1796-1808.
[19] Wensveen FM,Valentic S,Sestan M,et al. The "Big Bang" in obese fat:Events initiating obesity-induced adipose tissue inflammation [J]. Eur J Immunol,2015,45(9):2446-2456.
[20] Liu Y,Chen Y,Zhang J,et al. Retinoic acid receptor-related orphan receptor alpha stimulates adipose tissue inflammation by modulating endoplasmic reticulum stress [J]. J Biol Chem,2017,292(34):13 959-13 969.
[21] Chylikova J,Dvorackova J,Tauber Z,et al. M1/M2 macr-ophage polarization in human obese adipose tissue [J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2018.
[22] Suzuki T,Gao J,Ishigaki Y,et al. ER stress protein CHOP mediates insulin resistance by modulating adipose tissue macrophage polarity [J]. Cell Rep,2017,18(8):2045-2057.
[23] Wang N,Guo J,Liu F,et al. Depot-specific inflammation with decreased expression of ATM2 in white adipose tissues induced by high-margarine/lard intake [J]. PLoS One,2017,12(11):e0188007.
[24] Williams H,Cassorla G,Pertsoulis N,et al. Human classical monocytes display unbalanced M1/M2 phenotype with increased atherosclerotic risk and presence of disease [J]. Int Angiol,2017,36(2):145-155.
[25] Shirai T,Hilhorst M,Harrison DG,et al. Macrophages in vascular inflammation--From atherosclerosis to vasculitis [J]. Autoimmunity,2015,48(3):139-151.
[26] Seimon TA,Nadolski MJ,Liao X,et al. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress [J]. Cell Metab,2010,12(5):467-482.
[27] Santanam N,Elitsur Y,Stanek R,et al. Association between retinol binding protein 4 with atherosclerotic markers in obese children [J]. Minerva Endocrinol,2016,41(3):291-297.
[28] Dutta P,Nahrendorf M. Regulation and consequences of monocytosis [J]. Immunol Rev,2014,262(1):167-178.
[29] Engin A. The Pathogenesis of Obesity-Associated adipose tissue inflammation [J]. Adv Exp Med Biol,2017,960:221-245.
[30] Xie Z,Wang X,Liu X,et al. Adipose-Derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization [J]. J Am Heart Assoc,2018,7(5):e007442.
[31] Engin AB. Adipocyte-Macrophage Cross-Talk in Obesity [J]. Adv Exp Med Biol,2017,960:327-343.
[32] Sanada Y,Kumoto T,Suehiro H,et al. RASSF6 expression in adipocytes is down-regulated by interaction with macrophages [J]. PLoS One,2013,8(4):e61931.
[33] Sanada Y,Kumoto T,Suehiro H,et al. IkappaB kinase epsilon expression in adipocytes is upregulated by interaction with macrophages [J]. Biosci Biotechnol Biochem,2014,78(8):1357-1362.
[34] Chen J, Zhang M,Zhu M,et al. Paeoniflorin prevents endoplasmic reticulum stress-associated inflammation in lipopolysaccharide-stimulated human umbilical vein endothelial cells via the IRE1alpha/NF-kappaB signalingpathway [J]. Food Funct,2018,9(4):2386-2397.
[35] Hida K,Wada J,Eguchi J,et al. Visceral adipose tissue-derived serine protease inhibitor:a unique insulin-sensitizing adipocytokine in obesity [J]. Proc Natl Acad Sci USA,2005,102(30):10 610-10 615.
[36] Chang HM,Lee HJ,Park HS,et al. Effects of weight reduction on serum vaspin concentrations in obese subjects:modification by insulin resistance [J]. Obesity (Silver Spring),2010,18(11):2105-2110.
[37] Hida K,Poulsen P,Teshigawara S,et al. Impact of circulating vaspin levels on metabolic variables in elderly twins [J]. Diabetologia,2012,55(2):530-532.
[38] Nakatsuka A,Wada J,Iseda I,et al. Visceral adipose tissue-derived serine proteinase inhibitor inhibits apoptosis of endothelial cells as a ligand for the cell-surface GRP78/voltage-dependent anion channel complex [J]. Circ Res,2013,112(5):771-780.
[39] Lin Y,Zhuang J,Li H,et al. Vaspin attenuates the progression of atherosclerosis by inhibiting ER stress-induced macrophage apoptosis in apoE/ mice [J]. Mol Med Rep,2016,13(2):1509-1516.
[1]
黄蕊 黄永 刘兴钊 何玲. 血清ox-LDL、AIP水平与急性脑梗死患者颈动脉内膜中层厚度的关系 [J]. 中国医药导报, 2018, 15(4): 61-64.
[2]
张海涛 林文勇 王肖龙 解曼曼 王英杰. lncRNA与心血管疾病的研究进展 [J]. 中国医药导报, 2018, 15(31): 53-55,59.
[3]
张渊 邓舒昊 朱一成 江泉. 超声造影对颈动脉粥样硬化斑块稳定性及新生血管的评估价值研究 [J]. 中国医药导报, 2018, 15(28): 142-145.
[4]
徐丽英1 钟萍2 曹烨民1. 脂联素与糖尿病及其并发症的关系研究 [J]. 中国医药导报, 2018, 15(28): 29-32.
[5]
张文将1,2 易健1 刘柏炎1. 动脉粥样硬化炎症相关信号转导通路的研究进展 [J]. 中国医药导报, 2018, 15(27): 30-33,37.
[6]
李丽娟1 王庆高2 何亚州1 梁珊1 黄彩依1. lncRNA在动脉粥样硬化病变中的作用研究进展 [J]. 中国医药导报, 2018, 15(24): 22-25.
[7]
高逸之1 董成林1 左权2 钱紫娟3 李婉青1 张慧1 田晓利1 李仁杰1. 叶酸、VitB12对老年高同型半胱氨酸血症脑梗死伴颈动脉粥样硬化患者Cys C、Hcy、SOD表达的影响 [J]. 中国医药导报, 2018, 15(23): 88-91,95.
[8]
付广芳 吴敏 梁嘉琪. 经皮冠状动脉介入治疗患者心理状态及心理护理研究进展 [J]. 中国医药导报, 2018, 15(2): 39-42,53.
[9]
赵红梅 王颖 宋爱霞 李林儒 徐雪霞 刘星亮. 血管内低频高能超声消融术对动脉粥样硬化斑块的治疗影响 [J]. 中国医药导报, 2018, 15(19): 79-82,95.
[10]
王慧1 刘勤江2. ATF4基因与肿瘤 [J]. 中国医药导报, 2018, 15(18): 36-39.
[11]
李健兵1 杨建全2. 长期有氧运动联合桂枝茯苓胶囊治疗高血压颈动脉粥样硬化的临床效果 [J]. 中国医药导报, 2018, 15(17): 40-43.
[12]
孙晶1 王巍2 田野2 田振1▲. 内质网应激相关活性氧及其机制 [J]. 中国医药导报, 2018, 15(16): 42-44,54.
[13]
陈徐亮 周野 杨鹏麟. 实验性家兔颈动脉粥样硬化模型中颈动脉I/M值与肾动脉粥样硬化的相关性研究 [J]. 中国医药导报, 2018, 15(11): 12-16.
[14]
许继文1 李金霞2 张华敏3▲. 中医药调控心血管疾病自噬研究进展 [J]. 中国医药导报, 2018, 15(10): 38-41.
[15]
陈孝强 杨汉东 陈俊. 血清C1q、超敏C反应蛋白与冠状动脉粥样硬化性心脏病的相关性研究 [J]. 中国医药导报, 2017, 14(35): 41-44,49.