Perivascular Adipose Tissue-Derived Adiponectin Inhibits Collar-Induced Carotid Atherosclerosis by Promoting Macrophage Autophagy

• Published in: PloS one Vol. 10; no. 5; p. e0124031
• Main Authors: Li, Changlong, Wang, Zhijian, Wang, Chunxiao, Ma, Qian, Zhao, Yingxin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.05.2015; Public Library of Science (PLoS)
• Subjects: Adiponectin; Adiponectin - genetics; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - transplantation; AKT protein; Alcohol; Animals; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - genetics; Apoptosis; Arteriosclerosis; Atherosclerosis; Atherosclerosis - etiology; Atherosclerosis - immunology; Atherosclerosis - metabolism; Autophagy; Body fat; Cardiology; Care and treatment; Carotid arteries; Carotid Arteries - pathology; Carotid artery; Cell death; Complications and side effects; Development and progression; Disease; Disease Models, Animal; Forkhead Box Protein O3; Forkhead Transcription Factors - metabolism; FOXO3 protein; Gene Expression Regulation; Gene Knockout Techniques; Heart; High fat diet; Hospitals; Immunoglobulins; Inflammation; Laboratories; Lipids; Macrophages; Macrophages - metabolism; Mice; Oxidative stress; Phagocytosis; Physiological aspects; Physiology; Proto-Oncogene Proteins c-akt - metabolism; Quantitative analysis; Rodents; Signal Transduction; Signaling; Smooth muscle; Stress response; Transplantation; Veins & arteries; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124031

Adiponectin (APN) secreted from perivascular adipose tissue (PVAT) is one of the important anti-inflammatory adipokines to inhibit the development of atherosclerosis, but the underlying mechanism has not been clarified. In this study, we aimed to elucidate how APN regulates plaque formation in atherosclerosis. To assess the role of APN secreted by PVAT in atherosclerosis progression, we performed PVAT transplantation experiments on carotid artery atherosclerosis model: ApoE knockout (ApoE-/-) mice with a perivascular collar placement around the left carotid artery in combination with a high-fat diet feeding. Our results show that the ApoE-/- mice with PVAT derived from APN knockout (APN-/-) mice exhibited accelerated plaque volume formation compared to ApoE-/- mice transplanted with wild-type littermate tissue. Conversely, autophagy in macrophages was significantly attenuated in ApoE-/- mice transplanted with APN-/- mouse-derived PVAT compared to controls. Furthermore, in vitro studies indicate that APN treatment increased autophagy in primary macrophages, as evidenced by increased LC3-I processing and Beclin1 expression, which was accompanied by down-regulation of p62. Moreover, our results demonstrate that APN promotes macrophage autophagy via suppressing the Akt/FOXO3a signaling pathway. Our results indicate that PVAT-secreted APN suppresses plaque formation by inducing macrophage autophagy.