Pugliese Giuseppe, Iacobini Carla, Ricci Carlo, Blasetti Fantauzzi Claudia, Menini Stefano
Clin Chem Lab Med. 2014 Oct;52(10):1413-23. doi: 10.1515/cclm-2014-0187.
Galectin-3 is a versatile molecule which exerts several and sometimes opposite functions in various pathophysiological processes. Recently, galectin-3 has gained attention as a powerful predictor of heart failure and mortality, thus becoming a useful prognostic marker in clinical practice. Moreover, though not specifically investigated in diabetic cohorts, plasma levels of galectin-3 correlated with the prevalence of diabetes and related metabolic conditions, thus suggesting that pharmacological blockade of this lectin might be successful for treating heart failure especially in subjects suffering from these disorders. Indeed, galectin-3 is considered not only as a marker of heart failure, but also as a mediator of the disease, due to its pro-fibrotic action, though evidence comes mainly from studies in galectin-3 deficient mice. However, these studies have provided contrasting results, with either attenuation or acceleration of organ fibrosis and inflammation, depending on the experimental setting and particularly on the levels of advanced glycation endproducts (AGEs)/advanced lipoxidation endproducts (ALEs), of which galectin-3 is a scavenging receptor. In fact, under conditions of increased AGE/ALE levels, galectin-3 ablation was associated with tissue-specific outcomes, reflecting the AGE/ALE-receptor function of this lectin. Conversely, in experimental models of acute inflammation and fibrosis, galectin-3 deficiency resulted in attenuation of tissue injury. There is a need for prospective studies in diabetic patients specifically investigating the relation of galectin-3 levels with complications and for further animal studies in order to establish the effective role of this lectin in organ damage before considering its pharmacological blockade in the clinical setting.
半乳糖凝集素-3是一种多功能分子，在各种病理生理过程中发挥多种功能，有时甚至发挥相反的作用。最近，半乳糖凝集素-3作为心力衰竭和死亡率的有力预测指标受到关注，因此成为临床实践中有用的预后标志物。此外，尽管尚未在糖尿病队列中进行专门研究，但半乳糖凝集素-3的血浆水平与糖尿病及相关代谢疾病的患病率相关，这表明对这种凝集素进行药物阻断可能成功治疗心力衰竭，尤其是在患有这些疾病的患者中。事实上，半乳糖凝集素-3不仅被视为心力衰竭的标志物，还被视为该疾病的介质，因为其具有促纤维化作用，不过证据主要来自对半乳糖凝集素-3缺陷小鼠的研究。然而，这些研究得出了相互矛盾的结果，根据实验设置，尤其是晚期糖基化终产物（AGEs）/晚期脂质氧化终产物（ALEs）的水平，器官纤维化和炎症可能会减轻或加重，而半乳糖凝集素-3是这些终产物的清除受体。实际上，在AGE/ALE水平升高的情况下，半乳糖凝集素-3缺失与组织特异性结果相关，反映了这种凝集素的AGE/ALE受体功能。相反，在急性炎症和纤维化的实验模型中，半乳糖凝集素-3缺乏导致组织损伤减轻。需要对糖尿病患者进行前瞻性研究，专门调查半乳糖凝集素-3水平与并发症的关系，并进行进一步的动物研究，以便在考虑在临床环境中对这种凝集素进行药物阻断之前，确定其在器官损伤中的有效作用。
