Huang Derong, Wen Qing, Su Yuchen, Li Xiumao
Department of Cardiovascular Surgery, Affiliated Hospital of Zunyi Medical University, Guizhou, China
Balkan Med J. 2025 Aug 13. doi: 10.4274/balkanmedj.galenos.2025.2025-6-25.
Cardiac fibrosis plays a critical role in the progression of chronic cardiovascular conditions, with mitochondrial dysfunction acting as a central mechanism underlying pathological myocardial fibrosis. Increasing research shows that microRNAs may modulate the fibrotic process by regulating mitochondrial function via various pathways.
To examine the involvement of miR-17-5p in modulating mitochondrial autophagy and alleviating pathological cardiac fibrosis.
Combined and study.
Expression levels of miR-17-5P and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) were measured in a mouse model of myocardial fibrosis induced by abdominal aortic constriction, as well as in cardiac fibroblasts (CFs) treated with angiotensin II. CFs were transiently transfected with a miR-17-5p mimic, the pcDNA3.1-BNIP3 plasmid, or both. Cell viability was evaluated using the CCK-8 colorimetric assay. The expression of fibrotic and autophagy-related markers was determined via quantitative real-time reverse transcription polymerase chain reaction and immunoblotting. Intracellular levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were also assessed.
Reduced myocardial miR-17-5p expression was associated with diminished left ventricular systolic function and increased collagen accumulation in heart tissue. , angiotensin II treatment led to decreased miR-17-5p expression, upregulated BNIP3, and excessive mitochondrial autophagy-evidenced by increased ROS, lowered ATP production, and elevated fibrosis-related markers. Rescue experiments demonstrated that miR-17-5p overexpression directly targeted the 3' untranslated region (3'-UTR) of BNIP3, significantly downregulating its expression, restoring mitochondrial balance, and decreasing collagen production. Conversely, BNIP3 overexpression counteracted the anti-fibrotic and mitochondrial-protective effects of miR-17-5p.
The miR-17-5p/BNIP3 signaling pathway modulates mitochondrial autophagy in CFs and plays a key role in fibrotic remodeling. This axis may serve as a promising therapeutic target for reducing cardiac fibrosis and slowing the progression of heart failure.
心脏纤维化在慢性心血管疾病进展中起关键作用，线粒体功能障碍是病理性心肌纤维化的核心机制。越来越多的研究表明，微小RNA可能通过多种途径调节线粒体功能来调控纤维化过程。
研究miR-17-5p在调节线粒体自噬和减轻病理性心脏纤维化中的作用。
联合研究。
在腹主动脉缩窄诱导的心肌纤维化小鼠模型以及用血管紧张素II处理的心脏成纤维细胞（CFs）中，检测miR-17-5P和BCL2/腺病毒E1B 19 kDa蛋白相互作用蛋白3（BNIP3）的表达水平。用miR-17-5p模拟物、pcDNA3.1-BNIP3质粒或两者对CFs进行瞬时转染。使用CCK-8比色法评估细胞活力。通过定量实时逆转录聚合酶链反应和免疫印迹法测定纤维化和自噬相关标志物的表达。还评估了细胞内活性氧（ROS）和三磷酸腺苷（ATP）水平。
心肌miR-17-5p表达降低与左心室收缩功能减弱和心脏组织中胶原积累增加有关。同样，血管紧张素II处理导致miR-17-5p表达降低、BNIP3上调以及过度的线粒体自噬，表现为ROS增加、ATP生成降低和纤维化相关标志物升高。挽救实验表明，miR-17-5p过表达直接靶向BNIP3的3'非翻译区（3'-UTR），显著下调其表达，恢复线粒体平衡并减少胶原产生。相反，BNIP3过表达抵消了miR-17-5p的抗纤维化和线粒体保护作用。
miR-17-5p/BNIP3信号通路调节CFs中的线粒体自噬，并在纤维化重塑中起关键作用。该轴可能是减少心脏纤维化和减缓心力衰竭进展的有前景的治疗靶点。
