sPLA2-IIA Augments Oxidized LDL-Induced MCP-1 Expression in Vitro Through Activation of Akt

Abstract

This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Key WordsAbstract 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-GFPsPLA2-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 realtime 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-1was 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.Y. Guo and B. Li contributed equally to the study.

Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase A2

“…Along with other inflammatory markers, namely interleukin 6 (IL-6) and C-reactive protein (CRP), the level of hGIIA sharply increases during the first four days after acute coronary syndrome (ACS) [ 81 ]. Potentiation of the effects of oxidized LDL has been observed to occur through hGIIA in a pro-atherogenic manner by the activation of smooth muscle cells and secreting monocyte chemoattractant protein-1 [ 82 ]. Plasma levels of hGIIA are closely related to the severity of the outcome in ACS patients, as it has been seen that the probability of being subject to another coronary event after unstable angina and percutaneous coronary intervention was significantly increased in the cohorts with an elevated hGIIA level [ 83 , 84 ].…”

Exploring the mechanism of atherosclerosis and the intervention of traditional Chinese medicine combined with mesenchymal stem cells based on inflammatory targets

“…Secretory phospholipase A2 of group IIA (sPLA2-IIA), an inflammatory protein, is activated through the PI3K/Akt pathway to increase ox-LDL-induced MCP-1 expression. It can also selectively activate the proinflammatory function in human aortic SMC, thereby exerting its AS effect [ [38] , [39] , [40] ]. In summary, PLA2 family members modify phospholipids to produce pro-inflammatory lipids that cause AS, and Lp-PLA2 and sPLA2-IIA are novel inflammatory markers for predicting and evaluating plaque instability in AS.…”

Secretory phospholipase A2: a biomarker of inflammation in autoimmune, bacterial and viral diseases

“…Фосфолипазы PLA2 гидролизуют в положении sn-2 фосфолипиды плазматической и мембраны митохондрий с образованием лизофосфолипидов, арахидоновой (АК), лизофосфатидной кислот, простагландинов, лейкотриенов, тромбоксана, фактора активации тромбоцитов и неэтерифицированных жирных кислот [28,29,30] (рис. 2).…”