Abstract 188: Angiopoietin-Like Protein 4 is a HDL Component For HDL Metabolism snd Function in Non-Diabetic Participants and Type-2 Diabetic Patients

Abstract

Objectives: Angiopoietin-like protein 4 (angptl4) is a potent lipoprotein lipase inhibitor and present in HDLs in mice and human. Plasma levels of ANGPTL4 were increased in type-2 diabetic (T2DM) patients. However, it is not defined whether ANGPTL4 in HDLs could participate in HDL metabolism and affect its function in T2DM. Methods: Non-diabetic (n=201) and T2DM patients (n=185) were analyzed in the study. Angptl4 levels in the circulation and HDLs were quantified by ELISA. HDL components were measured. HDLs were isolated to assess cholesterol efflux or subjected to endothelial lipase (EL)-expressing HEK293 cells to study the kinetic of EL hydrolysis in vitro . Results: The levels of angptl4 in the plasma and HDLs were 1.7- and 2.0-fold higher in T2DM patients than non-diabetic controls (p<0.0001 for both). When angptl4-containing HDLs were subjected onto HEK 293 cells expressing EL, phospholipid and triglyceride were dramatically hydrolyzed in HDLs with medium- and high-levels of angptl4 when compared with those having lowest angptl4 levels in HDLs in T2DM patients (p<0.05 for phospholipid; p<0.01 for triglyceride), but it did not occur in HDLs isolated from healthy controls (p>0.62 for both).Cholesterol hydrolysis was comparable and independent of angptl4 levels in HDLs in both groups. Multivariate-adjusted analysis demonstrated that per one doubling increase of ANGPTL4 levels in HDLs, the changes amounted to +0.27% cholesterol efflux (p=0.03), +0.06 μg/mL apoA-I (p=0.09) and -9.41 μg/L SAA (p=0.02) in non-diabetic controls. In T2DM patients, the corresponding estimates were -0.06% cholesterol efflux (p=0.10), -0.06 μg/mL apoA-I (p=0.38) and +3.64 μg/L SAA (p=0.72). Conclusions: Angptl4 in HDLs protected HDLs from hydrolysis and maintained HDL function in non-diabetic controls. Resulting from increased circulating angptl4 levels in T2DM, angptl4 levels in HDLs were elevated that compromised its inhibitory effect on EL, leading to increased HDL hydrolysis and dysfunction.