PMID- 26488172 OWN - NLM STAT- MEDLINE DCOM- 20160822 LR - 20211203 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 37 IP - 4 DP - 2015 TI - sPLA2-IIA Augments Oxidized LDL-Induced MCP-1 Expression in Vitro Through Activation of Akt. PG - 1345-54 LID - 10.1159/000430255 [doi] AB - BACKGROUND/AIMS: Group IIA secretory phospholipase A2 (sPLA2-IIA) has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. METHODS: Human aortic smooth muscle cells (HASMCs) were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP). Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL), sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002. The mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) were assessed by quantitative real-time polymerase chain reaction (QRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Phosphorylation of Akt was examined by western blotting. RESULTS: Lv-GFP-sPLA2-IIA-transduced HASMCs remained fluorescent during 72 h of the study period with infection ratio of around 80%. The mRNA expression and protein secretion of MCP-1 was not altered in groups of HASMCs, Lv-GFP transduced and Lv-GFP-sPLA2-IIA-transduced HASMCs (p>0.05), but was significantly increased in the presence of oxidized LDL especially in Lv-GFP-sPLA2-IIA transduction group (p<0.01). However, with the addition of LY315920, this enhancement was notably decreased (p<0.05). This enhancement was also markedly abolished by co-incubation with LY294002, paralleled with suppressed Akt phosphorylation. CONCLUSIONS: Overexpression of sPLA2-IIA does not alter MCP-1 level at baseline, but could enhance the atherogenic effect of oxidized LDL in HASMCs, at least partly due to activation of Akt. These findings may provide a strategy for treatment of inflammatory cardiovascular diseases. CI - (c) 2015 S. Karger AG, Basel. FAU - Guo, Yongjun AU - Guo Y FAU - Li, Bo AU - Li B FAU - Xu, Xuejing AU - Xu X FAU - Wu, Rong AU - Wu R FAU - Li, Weihua AU - Li W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151022 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Acetates) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chromones) RN - 0 (Indoles) RN - 0 (Keto Acids) RN - 0 (Lipoproteins, LDL) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (oxidized low density lipoprotein) RN - 0NB98NBX3D (varespladib methyl) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.1.4 (Group II Phospholipases A2) SB - IM MH - Acetates/pharmacology MH - Cell Line MH - Chemokine CCL2/*metabolism MH - Chromones/pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression/drug effects MH - Genes, Reporter MH - Group II Phospholipases A2/antagonists & inhibitors/genetics/*metabolism MH - HEK293 Cells MH - Humans MH - Indoles/pharmacology MH - Keto Acids MH - Lipoproteins, LDL/*toxicity MH - Morpholines/pharmacology MH - Myocytes, Smooth Muscle/cytology/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism MH - RNA, Messenger/metabolism EDAT- 2015/10/22 06:00 MHDA- 2016/08/23 06:00 CRDT- 2015/10/22 06:00 PHST- 2015/08/31 00:00 [accepted] PHST- 2015/10/22 06:00 [entrez] PHST- 2015/10/22 06:00 [pubmed] PHST- 2016/08/23 06:00 [medline] AID - 000430255 [pii] AID - 10.1159/000430255 [doi] PST - ppublish SO - Cell Physiol Biochem. 2015;37(4):1345-54. doi: 10.1159/000430255. Epub 2015 Oct 22.