Integrin beta 3 Deficiency Results in Hypertriglyceridemia via Disrupting LPL (Lipoprotein Lipase) Secretion
文献类型：期刊论文
| 作者 | Xiao, Bing1,2; Mao, Jianhua3; Sun, Boyang5; Zhang, Wei3; Wang, Yun3; Wang, Pengran3; Ruan, Zheng3; Xi, Wenda4; Li, Huiyuan5; Zhou, Jingyi6 |
| 刊名 | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
 |
| 出版日期 | 2020-05-01 |
| 卷号 | 40期号:5页码:1296-1310 |
| ISSN号 | 1079-5642 |
| 关键词 | integrins lipoprotein lipase lipoproteins protein kinase D thrombasthenia |
| DOI | 10.1161/ATVBAHA.119.313191 |
| 通讯作者 | Shi, Xiaofeng(shixiaofeng1977@163.com) ; Yang, Renchi(rcyang65@163.com) ; Xi, Xiaodong(xixiaodong@shsmu.edu.cn) |
| 英文摘要 | Objective: Integrin beta 3 is implicated in numerous biological processes such as its relevance to blood triglyceride, yet whether beta 3 deficiency affects this metabolic process remains unknown. Approach and Results: We showed that the Chinese patients with beta 3-deficient Glanzmann thrombasthenia had a 2-fold higher serum triglyceride level together with a lower serum LPL (lipoprotein lipase) level than those with an alpha IIb deficiency or healthy subjects. The beta 3 knockout mice recapitulated these phenotypic features. The elevated plasma triglyceride level was due to impaired LPL-mediated triglyceride clearance caused by a disrupted LPL secretion. Further analysis revealed that beta 3 directly bound LPL via a juxtamembrane TIH (threonine isoleucine histidine)(720)(-722) motif in its cytoplasmic domain and functioned as an adaptor protein by interacting with LPL and PKD (protein kinase D) to form the PKD/beta 3/LPL complex that is required for beta 3-mediated LPL secretion. Furthermore, the impaired triglyceride clearance in beta 3 knockout mice could be corrected by adeno-associated virus serotype 9 (AAV9)-mediated delivery of wild-type but not TIH720-722-mutated beta 3 genes. Conclusions: This study reveals a hypertriglyceridemia in both beta 3-deficient Chinese patients and mice and provides novel insights into the molecular mechanisms of the significant roles of beta 3 in LPL secretion and triglyceride metabolism, drawing attention to the metabolic consequences in patients with beta 3-deficient Glanzmann thrombasthenia. |
| WOS关键词 | PROTEIN-KINASE-D ; GLANZMANN-THROMBASTHENIA ; MICE LACKING ; HEPATIC LIPASE ; ADIPOSE-TISSUE ; METABOLISM ; INSULIN ; ALPHA(IIB)BETA(3) ; RECEPTOR ; INHIBITION |
| 资助项目 | National Natural Science Foundation of China[81970112] ; National Natural Science Foundation of China[81670127] ; National Natural Science Foundation of China[81700130] ; National Natural Science Foundation of China[81101721] ; Science and Technology Commission of Shanghai Municipality[16PJ1406100] ; Science and Technology Commission of Shanghai Municipality[16ZR1421000] ; Natural Science Foundation of Jiangsu Province[BK20150474] ; Science and Technology Commission of Zhenjiang Municipality[SH2017006] ; CAMS Innovation Fund for Medical Sciences (CIFMS)[2016-I2M-1-002] |
| WOS研究方向 | Hematology ; Cardiovascular System & Cardiology |
| 语种 | 英语 |
| 出版者 | LIPPINCOTT WILLIAMS & WILKINS |
| WOS记录号 | WOS:000529958300030 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280592]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shi, Xiaofeng; Yang, Renchi; Xi, Xiaodong |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, State Key Lab Med Genom, Shanghai Inst Hematol, Collaborat Innovat Ctr Hematol,Ruijin Hosp,Sch Me, Shanghai 200025, Peoples R China 3.Shanghai Jiao Tong Univ, State Key Labo Med Genom, Shanghai Inst Hematol, Ruijin Hosp,Sch Med, Shanghai, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Hypertens, Ruijin Hosp, Shanghai, Peoples R China 5.Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Hematol Disorders, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China 6.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Lab Med, Shanghai, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Beijing, Peoples R China 8.Dalian Med Univ, Liaoning Key Lab Hematopoiet Stem Cell Transplant, Dept Hematol, Hosp 2, Dalian, Peoples R China 9.Jiangsu Univ, Affiliated Hosp, Dept Hematol, Zhenjiang 212001, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiao, Bing,Mao, Jianhua,Sun, Boyang,et al. Integrin beta 3 Deficiency Results in Hypertriglyceridemia via Disrupting LPL (Lipoprotein Lipase) Secretion[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2020,40(5):1296-1310. |
| APA | Xiao, Bing.,Mao, Jianhua.,Sun, Boyang.,Zhang, Wei.,Wang, Yun.,...&Xi, Xiaodong.(2020).Integrin beta 3 Deficiency Results in Hypertriglyceridemia via Disrupting LPL (Lipoprotein Lipase) Secretion.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,40(5),1296-1310. |
| MLA | Xiao, Bing,et al."Integrin beta 3 Deficiency Results in Hypertriglyceridemia via Disrupting LPL (Lipoprotein Lipase) Secretion".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 40.5(2020):1296-1310. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。