Related Experiment Video
Updated: Jul 10, 2026
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
TRIM65 accelerates VSMC-derived foam cell formation and arteriosclerosis progression by inhibiting mitophagy
Liyuan Guo1, Wei Deng1, Zhixiang Zhou1
1Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, 421001, Hunan, PR China.
Abstract:
Atherosclerosis (AS) is a chronic inflammatory vascular disorder driven by dyslipidemia and characterized by foam cell formation originating from vascular smooth muscle cells (VSMCs). Mitophagy is a critical pathway for the selective clearance of dysfunctional mitochondria and also contributes to macrophage foaming. Tripartite motif-containing protein 65 (TRIM65), a key protein within the TRIM family, plays a significant role in immune and inflammatory responses and is integral to the pathogenesis of AS. In vivo and in vitro models of as were established using ApoE-/- mice fed a high-fat diet and mouse aortic vascular smooth muscle (MOVAS) cells treated with oxidized low-density lipoprotein (ox-LDL), respectively. Results indicated a significant increase in TRIM65 expression in atherosclerotic models. The generation of TRIM65-/-ApoE-/- mice demonstrated that TRIM65 knockdown reduced atherosclerotic plaque burden and lipid accumulation. In vitro experiments revealed that TRIM65 knockdown inhibited the formation of VSMC-derived foam cells while promoting mitochondrial autophagy. Mechanistic investigations showed that TRIM65 facilitates the degradation of key mitochondrial autophagy proteins (e.g., PINK1, Parkin), thereby inhibiting mitochondrial autophagy. This inhibition leads to the accumulation of dysfunctional mitochondria, resulting in excessive ROS generation and exacerbating oxidative stress. By inhibiting mitochondrial autophagy, TRIM65 accelerates the formation of VSMC-derived foam cells, thereby promoting the onset and progression of as. This discovery not only deepens our understanding of the molecular mechanisms of as but also provides theoretical support for positioning TRIM65 as a potential novel therapeutic target for the prevention and treatment of this disease.
Insights
Tripartite motif-containing protein 65 (TRIM65) promotes atherosclerosis by inhibiting mitochondrial autophagy, leading to foam cell formation. Reducing TRIM65 expression could be a therapeutic strategy for atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Biology
Background:
- Atherosclerosis (AS) is a chronic inflammatory vascular disease characterized by lipid-driven foam cell formation from vascular smooth muscle cells (VSMCs).
- Mitophagy, the clearance of damaged mitochondria, is crucial for cellular health and implicated in macrophage foam cell formation.
- Tripartite motif-containing protein 65 (TRIM65) is involved in inflammatory responses and its role in AS pathogenesis is under investigation.
Purpose of the Study:
- To investigate the role of TRIM65 in the development and progression of atherosclerosis.
- To elucidate the molecular mechanisms by which TRIM65 influences VSMC-derived foam cell formation and mitochondrial autophagy in AS.
Main Methods:
- Establishment of in vivo (ApoE-/- mice on high-fat diet) and in vitro (MOVAS cells with ox-LDL) atherosclerosis models.
- Generation of TRIM65-/-ApoE-/- mice to assess TRIM65's in vivo function.
- Assessment of TRIM65 expression, atherosclerotic plaque burden, lipid accumulation, foam cell formation, and mitochondrial autophagy markers (PINK1, Parkin).
Main Results:
- TRIM65 expression was significantly elevated in atherosclerotic models.
- TRIM65 deficiency reduced atherosclerotic plaque burden and lipid accumulation in vivo.
- TRIM65 knockdown inhibited VSMC-derived foam cell formation and promoted mitochondrial autophagy in vitro.
- TRIM65 was found to promote the degradation of PINK1 and Parkin, thereby inhibiting mitochondrial autophagy and increasing ROS production.
Conclusions:
- TRIM65 exacerbates atherosclerosis by inhibiting mitochondrial autophagy, leading to dysfunctional mitochondria, oxidative stress, and VSMC-derived foam cell formation.
- TRIM65 acts as a pro-atherogenic factor by disrupting mitochondrial quality control.
- TRIM65 represents a potential novel therapeutic target for preventing and treating atherosclerosis.
Related Concept Videos
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:38Inflammation
01:30Apoptosis