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Updated: Feb 23, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
MicroRNA-134 Promotes the Development of Atherosclerosis Via the ANGPTL4/LPL Pathway in Apolipoprotein E Knockout
Qiong Ye1,2,3, Guo-Ping Tian2, Hai-Peng Cheng1
1Institute 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.
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.
Insights
MicroRNA-134 (miR-134) accelerates atherosclerosis by increasing lipid buildup and inflammation via the ANGPTL4/LPL pathway. Targeting miR-134 may help treat cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- Atherosclerosis, a leading cause of heart attack and stroke, involves lipid accumulation and inflammation.
- Previous research indicated microRNA-134 (miR-134) promotes lipid and inflammatory responses in macrophages via ANGPTL4/LPL signaling.
Purpose of the Study:
- To investigate the in vivo role of miR-134 in accelerating atherosclerosis.
- To elucidate the underlying molecular mechanisms involving ANGPTL4/LPL signaling.
Main Methods:
- Apolipoprotein E knockout (ApoE KO) mice were fed a high-fat diet and treated with miR-134 agomir or antagomir.
- Evaluated aortic atherosclerosis, lipid levels, inflammatory markers, and ANGPTL4/LPL pathway components.
Main Results:
- miR-134 agomir administration significantly increased atherosclerotic lesion size, inflammation, and macrophage lipid content.
- Overexpression of miR-134 reduced ANGPTL4 but increased LPL expression and activity, promoting LPL/LRP1 complex formation.
- miR-134 antagomir exhibited opposite effects, reducing atherosclerosis progression.
Conclusions:
- miR-134 promotes atherogenesis by enhancing lipid accumulation and inflammation through the ANGPTL4/LPL pathway.
- Targeting miR-134 presents a potential therapeutic strategy for atherosclerotic cardiovascular diseases.
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