髓过氧化物酶
载脂蛋白E
炎症
胆固醇
内科学
医学
病变
中性粒细胞胞外陷阱
泡沫电池
内分泌学
单核细胞
骨髓
免疫学
活性氧
化学
疾病
病理
脂蛋白
生物化学
作者
Keita Yamamoto,Hiroyuki Yamada,Noriyuki Wakana,Masakazu Kikai,Kensuke Terada,Naotoshi Wada,Shinichiro Motoyama,Makoto Saburi,T Sugimoto,Daisuke Kami,Takehiro Ogata,Masakazu Ibi,Chihiro Yabe‐Nishimura,Satoaki Matoba
标识
DOI:10.1016/j.bbrc.2018.04.115
摘要
Depression is an independent risk factor of cardiovascular disease (CVD); however, the causal association remains undefined. We exposed mice to repeated social defeat (RSD) to precipitate depressive-like behaviors, and investigated the effects on atherosclerosis. Eight-week-old male apoE−/− mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days and fed a high-cholesterol diet (HCD) for 6 weeks. The social interaction ratio and immobility time showed dramatic social avoidance before and after HCD feeding. Defeated mice showed higher increase in atherosclerotic lesion areas in the aortic root and entire aorta than control mice. Mean blood pressure and lipid profile were equivalent in both groups. While Ly-6G- and Mac3-positive areas in the aortic root were comparable between the groups, citrullinated histone H3 (Cit-H3)- and myeloperoxidase (MPO)-positive areas, markers of neutrophil extracellular traps (NETs), were significantly increased in the defeated mice. Treatment with DNase I completely diminished the exaggerated atherosclerosis. The proportion of peripheral blood polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), but not of inflammatory monocytes, was markedly increased. Moreover, in vitro NETs formation from bone marrow (BM) PMN-MDSC was markedly augmented, accompanied by higher expression of Nox2 gene and reactive oxygen species. Our findings demonstrate that exposure to RSD promotes atherosclerosis by augmenting NETs formation within the plaque. This provides new insight into the underlying mechanism of depression-related CVD.
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