Frunza Olga, Russo Ilaria, Saxena Amit, Shinde Arti V, Humeres Claudio, Hanif Waqas, Rai Vikrant, Su Ya, Frangogiannis Nikolaos G
Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York.
Am J Pathol. 2016 May;186(5):1114-27. doi: 10.1016/j.ajpath.2015.12.017. Epub 2016 Mar 3.
The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response.
β-半乳糖苷结合性动物凝集素半乳凝素-3主要由活化的巨噬细胞表达，是心力衰竭患者一个很有前景的生物标志物。半乳凝素-3调节炎症和纤维化反应；然而，其在心脏重塑中的作用仍不清楚。我们推测半乳凝素-3可能在压力超负荷心肌中上调，并调节心肌肥厚和纤维化。在正常小鼠心肌中，半乳凝素-3在巨噬细胞中组成性表达，并定位于心房而非心室心肌细胞。在主动脉缩窄小鼠模型中，半乳凝素-3在压力超负荷心肌中表达明显上调。半乳凝素-3的早期上调定位于巨噬细胞和成肌纤维细胞亚群；然而，在主动脉缩窄7至28天后，纤维化区域的一部分心肌细胞含有大量半乳凝素-3。在体外，细胞因子刺激抑制巨噬细胞和心脏成纤维细胞合成半乳凝素-3。相关性研究表明，心肌细胞而非巨噬细胞特异性的半乳凝素-3定位与不良重塑和功能障碍有关。半乳凝素-3基因敲除小鼠在压力超负荷7天后出现加速的心肌肥厚，而雌性半乳凝素-3基因敲除小鼠在主动脉缩窄28天后出现延迟的心脏扩张。然而，半乳凝素-3缺失并不影响压力超负荷心脏的存活、收缩和舒张功能障碍、心脏纤维化以及心肌细胞肥大。尽管半乳凝素-3作为预后生物标志物具有潜在作用，但它不是心脏纤维化的关键调节因子，但可能会延迟肥厚反应。
