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AMP-activated protein kinase mediates the effects of lipoprotein-associated
phospholipase A2 on endothelial dysfunction in atherosclerosis
#MMPMID28413519
Yang L
; Cong HL
; Wang SF
; Liu T
Exp Ther Med
2017[Apr]; 13
(4
): 1622-1629
PMID28413519
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The present study aimed to investigate the effects of lipoprotein-associated
phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an in vitro cell model
of atherosclerosis, and to determine whether AMP-activated protein kinase (AMPK)
mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392
patients with coronary artery disease (CAD), including various sub-conditions,
were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In
addition, an in vitro model of atherosclerosis was established by exposing human
umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein
(oxLDL). SB-435495 was used to inhibit Lp-PLA2, and compound C was used to
suppress AMPK expression. Lp-PLA2, AMPK? and phosphorylated-AMPK? (T172)
expression in HUVECs were evaluated using western blot analysis. The
concentrations of nitric oxide (NO), endothelin 1 (ET-1), intercellular adhesion
molecule 1 (ICAM-1) and platelet/endothelial cell adhesion molecule 1 (PECAM-1)
in cell culture supernatant were determined using commercially available ELISA
kits. MTT assays were employed to indicate changes in cell viability. The current
study found the plasma Lp-PLA2 levels were elevated in the CAD patients with
stable angina pectoris, unstable angina pectoris, acute coronary syndromes and
acute myocardial infarction, compared with a healthy control population. In
addition, the in vitro results showed that Lp-PLA2 expression levels were
elevated in oxLDL-exposed HUVECs. Lp-PLA2 suppression could increase cell
viability, induce the production of NO and decrease the secretion of ET-1, in
addition to suppressing the expression of cell adhesion molecules, including
ICAM-1 and PECAM-1 in oxLDL-exposed HUVECs. The expression of AMPK? and
phosphorylated-AMPK? (T172) was regulated by Lp-PLA2, and AMPK suppression was
able to reverse the effects of Lp-PLA2 with regard to cell viability, endothelial
vasorelaxation capacity and the secretion of adhesion molecules in oxLDL-exposed
HUVECs. In conclusion, the present study provides initial evidence that Lp-PLA2
is able to cause endothelial dysfunction in an in vitro model of atherosclerosis,
and the effects of Lp-PLA2 on endothelial dysfunction was at least partially a
result of the downregulation of AMPK?, thus contributing to the progression of
atherosclerosis.
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