Abstract：
Glycation is a protein post-translational modification that can occur on lysine and arginine residues as a result of a non-enzymatic process known as the Maillard reaction. This modification is irreversible, so the only way it can be removed is by protein degradation and replacement. Small reactive carbonyl species, glyoxal and methylglyoxal, are the primary glycating agents and are elevated in several conditions associated with an increased risk of cardiovascular disease, including diabetes, rheumatoid arthritis, smoking, and aging. Thus, how protein glycation impacts the cardiomyocyte is of particular interest, to both understand how these conditions increase the risk of cardiovascular disease and how glycation might be targeted therapeutically. Glycation can affect the cardiomyocyte through extracellular mechanisms, including RAGE-based signaling, glycation of the extracellular matrix that modifies the mechanical environment, and signaling from the vasculature. Intracellular glycation of the cardiomyocyte can impact calcium handling, protein quality control and cell death pathways, as well as the cytoskeleton, resulting in a blunted contractility. While reducing protein glycation and its impact on the heart has been an active area of drug development, multiple clinical trials have had mixed results and these compounds have not been translated to the clinic-highlighting the challenges of modulating myocyte glycation. Here we will review protein glycation and its effects on the cardiomyocyte, therapeutic attempts to reverse these, and offer insight as to the future of glycation studies and patient treatment.
摘要：
糖基化是一种蛋白质翻译后修饰,其可作为称为美拉德反应的非酶促过程的结果而发生在赖氨酸和精氨酸残基上。这种修改是不可逆的,因此，唯一可以去除它的方法是通过蛋白质降解和替代。小的反应性羰基，乙二醛和甲基乙二醛，是主要的糖基化药物，并且在与心血管疾病风险增加相关的几种情况下升高，包括糖尿病,类风湿性关节炎,吸烟,和衰老。因此，蛋白质糖基化如何影响心肌细胞是特别感兴趣的，了解这些疾病如何增加心血管疾病的风险，以及如何在治疗上靶向糖化。糖基化可以通过细胞外机制影响心肌细胞，包括基于RAGE的信令，改变机械环境的细胞外基质的糖基化，和来自脉管系统的信号。心肌细胞的细胞内糖基化可以影响钙处理，蛋白质质量控制和细胞死亡途径，以及细胞骨架，导致收缩迟钝。虽然减少蛋白质糖基化及其对心脏的影响一直是药物开发的活跃领域，多项临床试验的结果好坏参半,这些化合物尚未应用于临床,突出了调节肌细胞糖化的挑战.在这里，我们将综述蛋白质糖基化及其对心肌细胞的影响，治疗尝试扭转这些，并提供对未来糖化研究和患者治疗的见解。
