Lin Cuiting, Zheng Qiang, Yu Haiyan, Wu Ting, Chen Lin, Lin Weihao, Pang Jianxin, Yang Yang
Department of Pharmacy, Pingshan Hospital, Southern Medical University, Shenzhen, Guangdong, China.
Department of Pharmacy, Pingshan District Peoples' Hospital of Shenzhen, Shenzhen, Guangdong, China.
Front Endocrinol (Lausanne). 2025 Apr 7;16:1504614. doi: 10.3389/fendo.2025.1504614. eCollection 2025.
Maintaining polyamines homeostasis is essential for cardiovascular health, whereas elevated uric acid levels are recognized as a significant risk factor for the onset and progression of cardiovascular diseases. However, the interaction between uric acid and the regulation of polyamine homeostasis has not been extensively investigated. The objective of this study was to investigate the influence of uric acid on cardiac polyamines regulation and elucidate the role of polyamines in uric acid induced cardiomyocytic injury.
The experiments utilized H9C2 cardiomyocytes, the hyperuricemic mouse model was established via potassium oxonate and hypoxanthine. Techniques included energy metabolomics, HPLC for polyamine quantification, qPCR, ELISA, immunofluorescence, and mitochondrial membrane potential assessment using JC-1 staining, MTT cell viability analysis.
Uric acid treatment can alter ornithine metabolism in cardiomyocytes, revealed a potential of shifting it from the traditional ornithine cycle towards the polyamine cycle. Both ODC1 and SAT1 protein levels were up-regulated in hyperuricemic mice indicated a dysorder of polyamines homostasis. A downregulation tendency of spermidine and spermine levels were observed in cardiomyocytes under uric acid treatment. Notably, exogenous supplementation with spermidine or spermine effectively mitigated the uric acid-induced decline in cardiomyocyte viability and mitochondrial membrane potential.
Uric acid disrupts polyamine homeostasis, leading to mitochondrial dysfunction and cardiomyocyte damage. Exogenous polyamine supplementation demonstrates therapeutic potential by preserving mitochondrial integrity. These findings unveil a potential mechanism underlying uric acid-induced cardiac injury and propose polyamine replenishment as a viable intervention strategy for hyperuricemia-related cardiovascular complications.
维持多胺稳态对心血管健康至关重要，而尿酸水平升高被认为是心血管疾病发生和发展的重要危险因素。然而，尿酸与多胺稳态调节之间的相互作用尚未得到广泛研究。本研究的目的是探讨尿酸对心脏多胺调节的影响，并阐明多胺在尿酸诱导的心肌细胞损伤中的作用。
实验采用H9C2心肌细胞，通过氧嗪酸钾和次黄嘌呤建立高尿酸血症小鼠模型。技术包括能量代谢组学、用于多胺定量的高效液相色谱法、实时定量聚合酶链反应、酶联免疫吸附测定、免疫荧光以及使用JC-1染色评估线粒体膜电位、MTT细胞活力分析。
尿酸处理可改变心肌细胞中的鸟氨酸代谢，显示出从传统鸟氨酸循环向多胺循环转变的潜力。高尿酸血症小鼠中鸟氨酸脱羧酶1（ODC1）和精氨酸琥珀酸转移酶1（SAT1）蛋白水平均上调，表明多胺稳态紊乱。在尿酸处理的心肌细胞中观察到亚精胺和精胺水平有下调趋势。值得注意的是，外源性补充亚精胺或精胺可有效减轻尿酸诱导的心肌细胞活力下降和线粒体膜电位降低。
尿酸破坏多胺稳态，导致线粒体功能障碍和心肌细胞损伤。外源性补充多胺通过维持线粒体完整性显示出治疗潜力。这些发现揭示了尿酸诱导心脏损伤的潜在机制，并提出多胺补充作为高尿酸血症相关心血管并发症的一种可行干预策略。
