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2017 ; 6
(6
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Angiopoietin-Like Protein 4 Is a High-Density Lipoprotein (HDL) Component for HDL
Metabolism and Function in Nondiabetic Participants and Type-2 Diabetic Patients
#MMPMID28645936
Yang LY
; Yu CG
; Wang XH
; Yuan SS
; Zhang LJ
; Lang JN
; Zhao D
; Feng YM
J Am Heart Assoc
2017[Jun]; 6
(6
): ä PMID28645936
show ga
BACKGROUND: ANGPTL4 (angiopoietin-like protein 4) is a LPL (lipoprotein lipase)
inhibitor and is present in high-density lipoprotein (HDL). However, it is not
defined whether ANGPTL4 in HDLs could affect HDL metabolism and function in type
2 diabetes mellitus (T2DM). METHODS AND RESULTS: ANGPTL4 levels in the
circulation and HDLs were quantified in nondiabetic participants (n=201, 68.7%
females) and T2DM patients (n=185, 66.5% females). HDLs were isolated from
nondiabetic controls and T2DM patients to assess cholesterol efflux or subjected
to endothelial lipase (EL)-overexpressed HEK293 cells for EL hydrolysis in vitro.
The association between ANGPTL4 in HDLs and HDL components and function was
analyzed in nondiabetic participants or diabetic patients, respectively. Plasma
or HDLs of ANGPTL4+/+ and ANGPTL4-/- mice was subjected for cholesterol efflux or
EL hydrolysis, respectively. ANGPTL4 levels in the plasma and HDLs were 1.7- and
2.0-fold higher in T2DM patients than nondiabetic controls, respectively
(P<0.0001). Multivariable analysis demonstrated that per 1 doubling increase of
ANGPTL4 levels in HDLs, the changes amounted to +0.27% cholesterol efflux
(P=0.03), +0.06 ?g/mL apolipoprotein A-I (P=0.09) and -9.41 ?g/L serum amyloid A
(P=0.02) in nondiabetic controls. In T2DM patients, the corresponding estimates
were -0.06% cholesterol efflux (P=0.10), -0.06 ?g/mL apolipoprotein A-I (P=0.38),
and +3.64 ?g/L serum amyloid A (P=0.72). HDLs isolated from ANGPTL4-/- mice
showed accelerated hydrolysis by EL and reduced cholesterol efflux compared with
ANGPTL4+/+ littermates. CONCLUSIONS: Physically, ANGPTL4 in HDLs protected HDLs
from hydrolysis. Resulting from increased circulating ANGPTL4 levels in T2DM,
ANGPTL4 levels in HDLs were elevated but with compromised inhibitory effect on
EL, leading to increased HDL hydrolysis and dysfunction.
|Angiopoietin-Like Protein 4/*blood/deficiency/genetics
[MESH]