Successful reduction of inflammatory responses and arachidonic acid\u2013cyclooxygenase 2 pathway in human pulmonary artery endothelial cells by silencing adipocyte fatty acid-binding protein

Qian Wang,Caixin Zhang,Ying Teng,Qin Shen,Guanglin Shi,Xia Li,Jin Xie,Songshi Ni,Zhiyuan Tang

doi:10.1186/s12950-017-0155-6

Abstract

BackgroundAdipocyte fatty acid-binding protein, also known as aP2 or fatty acid-binding protein 4 (FABP4), plays an important role in inflammatory and metabolic responses in adipocytes and macrophages. Recent work has demonstrated that macrophage FABP4 integrates inflammatory and lipid metabolic responses, thereby contributing to the development of insulin resistance and atherosclerosis. However, it is not known whether FABP4 in human pulmonary artery endothelial cells(HPAECs) modulates inflammation.ResultsHere, we demonstrate that FABP4 and inflammatory cytokines are upregulated in lipopolysaccharide(LPS)-stimulated HPAECs. In addition, LPS increases the expression of molecules in the arachidonic acid(AA)–cyclooxygenase (COX) 2 signaling pathway in FABP4-expressing, but not FABP4-deficient, HPAECs.ConclusionsOur findings demonstrate that silencing FABP4 could decrease inflammatory cytokines, which were reported to be expressed via the AA–COX2 pathway, in HPAECs. In addition, silencing FABP4 could inhibit the expression of molecules in the AA–COX2 pathways. So we speculate silencing FABP4 could decrease the inflammatory response in HPAECs, which involves in the AA–COX2 signaling pathway. Our study suggests that FABP4 could be a potential biomarker and intervention point for the inflammation-related disease in HPAECs such as pulmonary thromboembolism.

Highlights

Adipocyte fatty acid-binding protein, known as aP2 or fatty acid-binding protein 4 (FABP4), plays an important role in inflammatory and metabolic responses in adipocytes and macrophages
FABP4 expression is associated with the inflammatory response and is increased in HPAECs by LPS treatment We found that levels of tumor necrosis factor-α (TNF-α), Interleukin-1 beta (IL-1β), and IL-6 are significantly higher in the serum of patients with Pulmonary thromboembolism (PTE) compared with healthy subjects (n = 20) (Fig. 1a), as measured by ELISA, and these inflammatory cytokines were reported to be expressed via the Arachidonic acid (AA)–Cyclooxygenase 2 (COX2) pathway [13, 14]
Using genomic and metabolomic approaches, we found that FABP4 is upregulated in animal models of PTE

Summary

Introduction

Adipocyte fatty acid-binding protein, known as aP2 or fatty acid-binding protein 4 (FABP4), plays an important role in inflammatory and metabolic responses in adipocytes and macrophages. Recent work has demonstrated that macrophage FABP4 integrates inflammatory and lipid metabolic responses, thereby contributing to the development of insulin resistance and atherosclerosis. It is not known whether FABP4 in human pulmonary artery endothelial cells(HPAECs) modulates inflammation. Vascular endothelial injury is the most important and common cause of thrombosis [1]. Accompanied by pulmonary artery endothelial injury and inflammatory reaction, pulmonary thromboembolism(PTE) would initiate and develop [3, 4]. PTE is a common illness, which caused by the obstruction of thrombus in pulmonary artery and its branches, with high mortality and morbidity [5]. There is an urgent need to identify accurate biomarkers to facilitate the early diagnosis of PTE

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