MicroRNA-134 Promotes the Development of Atherosclerosis Via the ANGPTL4/LPL Pathway in Apolipoprotein E Knockout Mice
Authors: Xiao-Hua Yu
Xiao-Dan Xia
Xiang Ou
Hai-Peng Cheng
Yan-Jun Pan
Chao-Ke Tang
Min Zhang
Wei Xie
Zhen-Wang Zhao
Qiong Ye
Ru-Qi Tan
Ling-Yan Chen
Jie Zhang
Xin Zhang
Chong Huang
Liang Li
Guo-Ping Tian
Xi-Long Zheng
Duo Gong
Feng-Yun Yang
Journal: Journal of Atherosclerosis and Thrombosis (2018)
Discipline: CLINICAL MEDICINE
Keywords: ANGPTL4; Atherosclerosis; LPL; MiR-134.
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China., Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China., Department of Ultrasound, Huadu District People's Hospital of Guangzhou., Department of Endocrinology, The First Hospital of Changsha., Department of Spinal Surgery, The Second Affiliated Hospital of University of South China., Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Health Sciences Center.

Abstract:  Aims: Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. Methods: ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/ low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. Results: Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. Conclusions: These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease. 

Retracted: No

PubPeer comments:
 Figure 1B. * Boxes of the same color highlight some unexpected similarities between the AG and AN-NC aortas. Could the authors please show some higher resolution photos of these samples, please, to take away any concern? ![file] , 
 Figure 1C The way in which the circles, squares, and triangles are arranged is exactly the same. They are just moved up and down along the vertical axis. Looks pretty disturbing. ![file] , 
 Retraction Note to: J Atheroscler Thromb, 2018; 25: 244-253 https: doi.org 10.5551 jat.40212 The Editorial Team of the Journal of Atherosclerosis and Thrombosis has recently confirmed that some data in the paper written by Qiong Ye et al., published in the Journal (J Atheroscler Thromb 2018; 25: 244-253), including the images of the mouse aorta and the graphs (Fig.1), are incorrect. Therefore, we have had to take the decision to retract the paper from the Journal of Atherosclerosis and Thrombosis with the agreement from the authors. ,