AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis

Yang,Li; Cong,Hong‑Liang; Wang,Shu‑Feng; Liu,Ting

doi:10.3892/etm.2017.4142

AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis

Authors:
- Li Yang
- Hong‑Liang Cong
- Shu‑Feng Wang
- Ting Liu
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Affiliations: Department of Cardiology, Thoracic Clinical College, Tianjin Medical University, Tianjin 300222, P.R. China, Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, P.R. China, Tianjin Cardiovascular Institute, Tianjin 300222, P.R. China
Published online on: February 21, 2017 https://doi.org/10.3892/etm.2017.4142
Pages: 1622-1629

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Abstract

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, AMPKα and phosphorylated‑AMPKα (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 AMPKα and phosphorylated‑AMPKα (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 AMPKα, thus contributing to the progression of atherosclerosis.

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