Hao Wen-Rui, Cheng Chun-Han, Chen Huan-Yuan, Cheng Tzu-Hurng, Liu Ju-Chi, Chen Jin-Jer
Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Ministry of Health and Welfare, Taipei Medical University, New Taipei City 23561, Taiwan.
Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11002, Taiwan.
Biomedicines. 2024 Dec 14;12(12):2847. doi: 10.3390/biomedicines12122847.
BACKGROUND/OBJECTIVES: Fucoidan, a sulfated polysaccharide derived from marine algae, is known for its antioxidant and immunomodulatory properties. Galectin-3 (Gal-3), a protein associated with cardiovascular fibrosis, has been identified as a potential therapeutic target in cardiac remodeling. This study aimed to evaluate whether fucoidan could inhibit Gal-3 activity and mitigate cardiac remodeling in a mouse model of pressure overload-induced cardiac hypertrophy.
To test this hypothesis, we used transverse aortic constriction (TAC) surgery to induce pressure overload in normotensive mice, replicating the pathological features of cardiac hypertrophy. Mice were treated with fucoidan at a dose of 1.5 or 7.5 mg/kg/day. In vivo assessments of cardiac function, fibrosis, inflammation, and Gal-3 expression were performed.
Pressure overload led to significant upregulation of serum Gal-3 levels, increased cardiac collagen deposition, and elevated markers of fibrosis and inflammation. In mice treated with fucoidan, these effects were significantly attenuated. Fucoidan treatment prevented the upregulation of Gal-3, reduced collagen deposition, and decreased inflammatory cell infiltration, suggesting an inhibition of both fibrosis and inflammation.
Fucoidan effectively mitigated the adverse effects of pressure overload in this mouse model, including reduced Gal-3 expression, fibrosis, and inflammation. These findings suggest that fucoidan holds promise as a therapeutic agent for preventing or delaying cardiac remodeling and associated complications, such as fibrosis and inflammation, in pressure overload-induced cardiac hypertrophy. Further research is needed to explore the underlying mechanisms and clinical applicability of fucoidan in cardiac disease.
背景/目的：岩藻依聚糖是一种从海藻中提取的硫酸化多糖，以其抗氧化和免疫调节特性而闻名。半乳糖凝集素-3（Gal-3）是一种与心血管纤维化相关的蛋白质，已被确定为心脏重塑的潜在治疗靶点。本研究旨在评估岩藻依聚糖是否能抑制Gal-3活性，并减轻压力超负荷诱导的心脏肥大小鼠模型中的心脏重塑。
为验证这一假设，我们采用横断主动脉缩窄（TAC）手术诱导正常血压小鼠出现压力超负荷，以复制心脏肥大的病理特征。小鼠以1.5或7.5mg/kg/天的剂量接受岩藻依聚糖治疗。对心脏功能、纤维化、炎症和Gal-3表达进行了体内评估。
压力超负荷导致血清Gal-3水平显著上调、心脏胶原沉积增加以及纤维化和炎症标志物升高。在用岩藻依聚糖治疗的小鼠中，这些影响显著减轻。岩藻依聚糖治疗可防止Gal-3上调，减少胶原沉积，并减少炎性细胞浸润，表明其对纤维化和炎症均有抑制作用。
岩藻依聚糖有效减轻了该小鼠模型中压力超负荷的不利影响，包括降低Gal-3表达、纤维化和炎症。这些发现表明，岩藻依聚糖有望作为一种治疗药物，用于预防或延缓压力超负荷诱导的心脏肥大中的心脏重塑及相关并发症，如纤维化和炎症。需要进一步研究以探索岩藻依聚糖在心脏病中的潜在机制和临床适用性。
