title: HDL in diabetic nephropathy has less effect in endothelial repairing than diabetes without complications.
abstract: BACKGROUND
  Diabetic nephropathy has a high cardiovascular risk with a low-level HDL(high density lipoprotein) in epidemiologic studies. Glycated HDL in diabetes can diminish the capacity to stimulate endothelial cell migration, but the mechanism has not been adequately explored in diabetic nephropathy. We performed this study to find out whether HDL in diabetic nephropathy is more dysfunctional than HDL in diabetes without complications.
  
  
  METHODS
  Endothelial cells were treated with N-HDL (normal), D-HDL (T2DM[type 2 diabetes mellitus] without complications), DN-HDL (T2DM nephropathy), N-apoA-I (normal apoA-I), and G-apoA-I (glycated apoA-I in vitro). Cell migration capacity was measured with wound-healing and transwell migration assay in vitro and electric carotid injury model in vivo. Protein glycation levels were measured with nanoLC-MS/MS. PI3K expression and Akt phosphorylation were analyzed by western blot.
  
  
  RESULTS
  In wound-healing assay, DN-HDL showed a 17.12% decrease compared with D-HDL (p < 0.05). DN-HDL showed a 29.85% decrease in comparison with D-HDL (p < 0.001) in transwell assay. In the electric carotid injury model, D-HDL and DN-HDL impaired the re-endothelialization capacity; DN-HDL was less effective than D-HDL. Meanwhile, DN-HDL was found to have a significantly higher protein glycation level than D-HDL (p < 0.001). PI3K expression and Akt phosphorylation were reduced significantly in DN-HDL in comparison with D-HDL and N-HDL.
  
  
  CONCLUSIONS
  We found that HDL from diabetic nephropathy has a higher level of glycation and induced less cell migration in vitro and in vivo compared with that from diabetes without nephropathy. This finding suggests that diabetic nephropathy has higher levels of glycated HDL and partially explains why patients with DN have a higher risk of cardiovascular disease.
authors.affiliation: Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen Nan Dajie, Xicheng District, Beijing, 100044, China.|Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing, 101200, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics, The Military General Hospital of Beijing, Beijing, 100700, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.affiliation: School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Huang
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ji
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Cleveland Clinic Lerner Research Institute Mass Spectrometry Laboratory for Protein Sequencing, Cleveland, Ohio, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.affiliation: Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing, 101200, China.
authors.forename: Zuodi
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing, 101200, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China. zhengl@bjmu.edu.cn.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen Nan Dajie, Xicheng District, Beijing, 100044, China. Jiln@bjmu.edu.cn.
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002465:Cell Movement; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008813:Mice, Inbred ICR; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D008075:Lipoproteins, HDL; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell migration; Diabetic nephropathy; Glycation; High density lipoprotein; Type 2 diabetes