PMID- 27620179 OWN - NLM STAT- MEDLINE DCOM- 20170213 LR - 20211204 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 15 IP - 1 DP - 2016 Sep 13 TI - Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients. PG - 132 LID - 10.1186/s12933-016-0450-1 [doi] LID - 132 AB - BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM). METHODS: We studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively. RESULTS: We demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 mug/mL apoA-I but decrease of 47.07 mug/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 mug/mL apoA-I but decrease of 11.70 mug/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors. CONCLUSIONS: ANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes. FAU - Zhao, Dong AU - Zhao D AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Yang, Long-Yan AU - Yang LY AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Wang, Xu-Hong AU - Wang XH AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Yuan, Sha-Sha AU - Yuan SS AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Yu, Cai-Guo AU - Yu CG AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Wang, Zong-Wei AU - Wang ZW AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Lang, Jia-Nan AU - Lang JN AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. FAU - Feng, Ying-Mei AU - Feng YM AD - Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing, 101149, China. yingmeif13@sina.com. AD - Stem Cell Institute, University of Leuven, 3000, Louvain, Belgium. yingmeif13@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160913 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (ANGPTL3 protein, human) RN - 0 (APOA1 protein, human) RN - 0 (Angiopoietin-Like Protein 3) RN - 0 (Angiopoietin-like Proteins) RN - 0 (Angiopoietins) RN - 0 (Angptl3 protein, mouse) RN - 0 (Apolipoprotein A-I) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Cholesterol, HDL) RN - 0 (Hypoglycemic Agents) RN - 0 (Hypolipidemic Agents) RN - 0 (Insulin) RN - 0 (Serum Amyloid A Protein) SB - IM MH - Adult MH - Age Factors MH - Angiopoietin-Like Protein 3 MH - Angiopoietin-like Proteins MH - Angiopoietins/*blood MH - Animals MH - Apolipoprotein A-I/blood MH - Biomarkers/blood MH - Blood Glucose/metabolism MH - Body Mass Index MH - Case-Control Studies MH - Cells, Cultured MH - Cholesterol, HDL/*blood MH - Diabetes Mellitus, Type 2/*blood/diagnosis/drug therapy MH - Disease Models, Animal MH - Down-Regulation MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Hepatocytes/metabolism MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Hypolipidemic Agents/therapeutic use MH - Insulin/therapeutic use MH - Linear Models MH - Male MH - Mice, Inbred C57BL MH - Middle Aged MH - Multivariate Analysis MH - Serum Amyloid A Protein/analysis MH - Sex Factors MH - Tertiary Care Centers PMC - PMC5020513 OTO - NOTNLM OT - Angiopoietin-like protein OT - Apolipoproteins OT - Cholesterol efflux OT - Diabetes OT - High-density lipoproteins OT - Serum amyloid A EDAT- 2016/09/14 06:00 MHDA- 2017/02/14 06:00 PMCR- 2016/09/13 CRDT- 2016/09/14 06:00 PHST- 2016/07/22 00:00 [received] PHST- 2016/09/03 00:00 [accepted] PHST- 2016/09/14 06:00 [entrez] PHST- 2016/09/14 06:00 [pubmed] PHST- 2017/02/14 06:00 [medline] PHST- 2016/09/13 00:00 [pmc-release] AID - 10.1186/s12933-016-0450-1 [pii] AID - 450 [pii] AID - 10.1186/s12933-016-0450-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2016 Sep 13;15(1):132. doi: 10.1186/s12933-016-0450-1.