著者

Shi-Lin Tang Zhen-Wang Zhao Shang-Ming Liu Gang Wang Xiao-Hua Yu Jin Zou Si-Qi Wang Xiao-Yan Dai Min-Gui Fu Xi-Long Zheng Da-Wei Zhang Hui Fu Chao-Ke Tang

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-18-0700, (Released:2019-01-18)

参考文献数

41

被引用文献数

25

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Background: Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis. Methods and Results: PAPP-A was silenced in apolipoprotein E (apoE−/−) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE−/−mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE−/−mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1β through the nuclear factor kappa-B (NF-κB) pathway. Conclusions: The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE−/−mice through reducing RCT capacity and activating an inflammatory response.