Journal
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
Volume 25, Issue 3, Pages 244-253Publisher
JAPAN ATHEROSCLEROSIS SOC
DOI: 10.5551/jat.40212
Keywords
MiR-134; ANGPTL4; LPL; Atherosclerosis
Categories
Funding
- National Natural Sciences Foundation of China [81570408, 81370377]
- Natural Science Foundation of Hunan Province [2015JJ2120, 2017JJ2286]
- construct program of the key discipline in Hunan province (Basic Medicine Sciences in University of South China, Xiangjiaofa) [[2011]76]
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [0223-0002-0002000-41, 0223-0002-0002000-42]
- Science and Technology Plan Project of Changsha City [KQ1602028]
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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.
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