MicroRNA-205-5p Promotes Unstable Atherosclerotic Plaque Formation In Vivo
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Updated: Dec 29, 2025
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Xiandong Meng1, Jianjiao Yin2, Xinli Yu3
1Department of Cardiology, The First People's Hospital of Keerqin District, No. 328, Keerqin Street, Keerqin District, Tongliao City, Inner Mongolia, China. 308740952@qq.com.
Purpose:
Atherosclerosis is a narrowing of the arteries caused by plaque buildup. MicroRNAs (miRNAs) have been proposed to participate in the pathogenesis of atherosclerosis. Here, we aimed to investigate miR-205-5p's role in promoting atherosclerotic progression.
Methods:
Knock-in (KI) mice with human/murine miR-205-5p within the murine host gene for miR-205 (MIR205HG) were crossed with apolipoprotein E knockout (Apoe-/-) mice. This miR-205KI Apoe-/- murine model was employed to study the impact of miR-205-5p in Apoe-/- mice susceptible to atherosclerotic plaque formation.
Results:
miR-205KI Apoe-/-mice developed larger, more unstable plaques relative to their Apoe-/- counterparts (0.45 vs. 0.26 mm2, P < 0.001). miR-205KI Apoe-/- mice exhibited lower serum levels of high-density lipoprotein cholesterol (HDL-C) (5.18 vs. 19.31 mg/dL, P < 0.001) and triglycerides (32.79 vs. 156.76 mg/dL, P < 0.001) with system-wide reversal of cholesterol transport. Macrophages derived from miR-205KI Apoe-/- mice exhibited ~ 20% lowered cholesterol efflux capability with enhanced pro-inflammatory gene expression through lipid raft formation. Bone marrow transplantation demonstrated that bone marrow (BM) donor cells with miR-205-5pKI simulated plaque formation independent of the recipients' miR-205-5p status.
Conclusions:
miR-205-5p encourages unstable atherogenesis in vivo. miR-205-5p also adversely influences lipid metabolism and promotes a pro-inflammatory macrophage phenotype. Our findings advocate miR-205-5p as a potential therapeutic target for combating unstable atherogenesis.
Insights
MicroRNA-205-5p (miR-205-5p) promotes unstable atherosclerosis by worsening lipid metabolism and macrophage inflammation. Targeting miR-205-5p may offer a new therapeutic strategy for treating atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genetics
Background:
- Atherosclerosis is a chronic inflammatory disease characterized by arterial plaque buildup.
- MicroRNAs (miRNAs) are implicated in the pathogenesis of atherosclerosis, regulating gene expression.
- The specific role of miR-205-5p in atherosclerotic progression requires further elucidation.
Purpose of the Study:
- To investigate the role of miR-205-5p in promoting the progression of atherosclerosis.
- To develop and utilize a novel murine model for studying miR-205-5p's effects on atherosclerosis.
Main Methods:
- Generation of miR-205-5p knock-in (KI) apolipoprotein E knockout (Apoe-/-) mice.
- Assessment of atherosclerotic plaque size and stability in the developed murine model.
- Analysis of serum lipid profiles, macrophage cholesterol efflux, and inflammatory gene expression.
Main Results:
- miR-205-5p KI Apoe-/- mice exhibited significantly larger and more unstable atherosclerotic plaques compared to controls.
- These mice showed dyslipidemia, characterized by lower HDL-C and triglyceride levels, and impaired cholesterol efflux in macrophages.
- Bone marrow transplantation studies confirmed that miR-205-5p expression in donor cells drives plaque formation.
Conclusions:
- miR-205-5p significantly promotes unstable atherogenesis in vivo.
- This microRNA adversely affects lipid metabolism and induces a pro-inflammatory macrophage phenotype.
- miR-205-5p emerges as a potential therapeutic target for combating unstable atherosclerosis.
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