期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1862, 期 12, 页码 1595-1605出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2017.09.009
关键词
omega-Alkynyl arachidonic acid; M2 macrophage polarization; Myocardial ischemia-reperfusion injury; PKM2; HIF-1a; iNOS
资金
- General Research Fund (GRF) from Research Grants Council (RGC) of Hong Kong, China [17120915, 17146216]
- internal Seed Funds for Basic Research Programme from University of Hong Kong, China [201511159245]
Macrophage polarization determines the timing for the switch from the inflammation phase to the inflammation resolution phase after acute myocardial infarction. The aim of the present study was to investigate whether omega-alkynyl arachidonic acid could mitigate the inflammatory lipid mediators in the regulation of macrophage phenotypes and functions with a special regard to myocardial infarction. We initially discovered that omega-alkynyl arachidonic acid selectively suppressed the up-regulation of inducible nitric oxide synthase (iNOS) over cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. omega-Alkynyl arachidonic acid also reduced the expression of macrophage M1 biomarkers (e.g., TNF-alpha, CXCL10, iNOS and IL-6) but increased the expression of macrophage M2 biomarkers (e.g., IL-10 and arginase-1) in LPS-stimulated macrophages. Moreover, omega-alkynyl arachidonic acid markedly enhanced the phagocytotic activity of macrophages against fluorescently-labeled beads or apoptotic H9c2 cardiac cells. We further investigated the in vivo cardioprotective activities of omega-alkynyl arachidonic acid in a mouse model of myocardial infarction. omega-Alkynyl arachidonic acid indeed reduced infarct size, cardiac damage and the leakage of myocardial enzymes CK-MB. Mechanistic studies revealed that omega-alkynyl arachidonic acid suppressed the overexpression and nuclear translocation of glycolytic enzyme PKM2 in LPS-stimulated macrophages. Furthermore, co-immunoprecipitation assay suggested that omega-alkynyl arachidonic acid disrupted the interaction between PKM2 and HIF-1 alpha. Consequently, omega-alkynyl arachidonic acid diminished HIF-1 alpha binding to the HRE sequence in iNOS promoter in response to LPS stimulation. Collectively, omega-alkynyl arachidonic acid may promote the anti-inflammatory M2 polarization of macrophages in acute myocardial infarction via regulating the cross-talk between PKM2, HIF-1 alpha and iNOS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据