Jiménez-González Sara, Delgado-Valero Beatriz, Romero-Miranda Ana, Islas Fabian, Luaces María, Ramchandani Bunty, Cuesta-Corral María, Montoro-Garrido Alejandro, Nieto María Luisa, Martínez-Martínez Ernesto, Cachofeiro Victoria
Departamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, Madrid, Spain.
Unidad de Imagen Cardíaca, Hospital General Universitario de Talavera de la Reina, Toledo, Spain.
Clin Investig Arterioscler. 2025 Jul-Aug;37(4):100750. doi: 10.1016/j.arteri.2024.10.007. Epub 2024 Dec 4.
Modified citrus pectin (MCP) is used as a nutritional supplement that inhibits galectin-3 activity, a central player in the cardiac damage associated with different pathological situations. In fact, we have previously observed that MCP improved cardiac function in obese infarcted rats that was associated with a reduction in cardiac fibrosis. Therefore, the aim of the present study was to further explore whether this effect could involve the modulation of gene expression of ECM components and their mediators as well as whether it could affect another two mechanisms involved in cardiac damage: mitochondrial dynamics and autophagic flux.
Male Wistar rats were fed an atherogenic diet with a high content of saturated fat (35%). MI was induced by the ligation of left anterior descendant (LAD) coronary artery 6 weeks after and MCP (100mg/kg/day) or vehicle were administered for 4 weeks more. A group of rats fed a standard diet (5.3% fat) and subjected to a sham operation was used as controls.
Obese infarcted animals presented an increase in cross-linked collagen that was not affected by the administration of galectin-3 inhibitor. However, MCP reduced the increase in gene expression observed in obese infarcted rats of ECM components and mediators (collagen I, fibronectin, transforming growth factor-β and connective tissue growth factor), of components of endoplasmic reticulum stress (binding immunoglobulin protein, CCAAT-enhancer-binding homologous protein and activating transcription factor 4), of oxidative stress mediator (NADPH oxidase-4) and normalized those of the interleukin 33/ST2 system. MCP is also able to increase the levels of the mitochondrial protein Dynamin-1-like and those of both proteins involved in autophagic flux (p62 and LC3) that were reduced by the myocardial ischemia in the context of obesity.
The data show that the beneficial effect of the nutritional supplement MCP on the cardiac consequences associated with myocardial ischemia in the context of obesity could rely on its capacity to inhibit galectin-3 and to consequently modulate different downstream mechanisms, including inflammation, ER stress, oxidative stress, autophagy and mitochondrial function, which can facilitate fibrosis and cardiac remodeling in this pathological context.
改性柑橘果胶（MCP）作为一种营养补充剂，可抑制半乳糖凝集素-3的活性，而半乳糖凝集素-3是与不同病理情况相关的心脏损伤的关键因素。事实上，我们之前观察到MCP可改善肥胖梗死大鼠的心脏功能，这与心脏纤维化的减轻有关。因此，本研究的目的是进一步探讨这种作用是否涉及细胞外基质（ECM）成分及其介质基因表达的调节，以及它是否会影响心脏损伤中涉及的另外两种机制：线粒体动力学和自噬通量。
雄性Wistar大鼠喂食富含饱和脂肪（35%）的致动脉粥样化饮食。6周后通过结扎左前降支（LAD）冠状动脉诱导心肌梗死（MI），随后MCP（100mg/kg/天）或溶剂再给药4周。一组喂食标准饮食（5.3%脂肪）并接受假手术的大鼠用作对照。
肥胖梗死动物的交联胶原增加，而给予半乳糖凝集素-3抑制剂对此无影响。然而，MCP降低了肥胖梗死大鼠中观察到的ECM成分和介质（I型胶原、纤连蛋白、转化生长因子-β和结缔组织生长因子）、内质网应激成分（结合免疫球蛋白蛋白、CCAAT增强子结合同源蛋白和激活转录因子4）、氧化应激介质（NADPH氧化酶-4）的基因表达增加，并使白细胞介素33/ST2系统的基因表达正常化。MCP还能够增加线粒体蛋白动力蛋白-1样蛋白的水平以及肥胖背景下心肌缺血降低的参与自噬通量的两种蛋白（p62和LC3）的水平。
数据表明，营养补充剂MCP对肥胖背景下与心肌缺血相关的心脏后果的有益作用可能依赖于其抑制半乳糖凝集素-3的能力，从而调节不同的下游机制，包括炎症、内质网应激、氧化应激、自噬和线粒体功能，这些机制在这种病理情况下可促进纤维化和心脏重塑。
