Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis.

Abstract

Increasing evidences showed that the survival of macrophages promotes atherogenesis. Macrophage apoptosis in the early phase of atherosclerotic process negatively regulates the progression of atherosclerotic lesions. We demonstrated that a natural anti-oxidant apigenin could ameliorate atherogenesis in ApoE(-/-) mice. It reduced the number of foam cells and decreased the serum levels of tumor necrosis factor α, interleukin 1β (IL-1β) and IL-6. Our results showed that oxidized low-density lipoprotein (oxLDL) led to the secretion of pro-inflammatory cytokines. Apigenin-induced apoptosis and downregulated the secretion of TNF-α, IL-6 and IL-1β. It is further supported by the use of zVAD, a pan-caspase inhibitor, demonstrating that apigenin lowered cytokine profile through induction of macrophage apoptosis. Moreover, apigenin-induced Atg5/Atg7-dependent autophagy in macrophages pretreated with oxLDL. Results illustrated that autophagy inhibition increased apigenin-induced apoptosis through activation of Bax. The present findings suggest that oxLDL maintained the survival of macrophages and activated the secretion of pro-inflammatory cytokines to initiate atherosclerosis. Apigenin-induced apoptosis of lipid-laden macrophages and resolved inflammation to ameliorate atherosclerosis. In conclusion, combination of apigenin with autophagy inhibition may be a promising strategy to induce foam cell apoptosis and subdue atherogenic cytokines.

• Authors: Qun Wang, Ping Zeng, Yuanliang Liu, Ge Wen, Xiuqiong Fu, Xuegang Sun
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 27 Issue 1 Pg. 24-31 (Jul 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25899084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Apolipoproteins E
• Cytokines
• Inflammation Mediators
• Lipoproteins, LDL
• Oligopeptides
• bcl-2-Associated X Protein
• benzyloxycarbonyl-valyl-alanyl-aspartic acid
• oxidized low density lipoprotein
• Apigenin

Topics

• Animals
• Apigenin (administration & dosage, adverse effects)
• Apolipoproteins E (genetics)
• Apoptosis (drug effects)
• Atherosclerosis (drug therapy, immunology)
• Autophagy (drug effects)
• Cells, Cultured
• Cytokines (blood)
• Inflammation (drug therapy, immunology)
• Inflammation Mediators (blood)
• Lipoproteins, LDL (metabolism)
• Macrophages (drug effects, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oligopeptides (administration & dosage)
• bcl-2-Associated X Protein (genetics, metabolism)