Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165729. doi: 10.1016/j.bbadis.2020.165729. Epub 2020 Feb 14.
Empagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been shown to reduce mortality and hospitalization for heart failure in diabetic patients in the EMPA-REG-OUTCOME trial (Zinman et al., 2015). Surprisingly, dapagliflozin, another SGLT2 inhibitor, exerted comparable effects on clinical endpoints even in the absence of diabetes mellitus (DAPA-HF trial) (McMurray et al., 2019). There is a myriad of suggested underlying mechanisms ranging from improved glycemic control and hemodynamic effects to altered myocardial metabolism, inflammation, neurohumoral activation and intracellular ion homeostasis. Here, we review the effects of gliflozins on cardiac electro-mechanical coupling with an emphasis on novel CaMKII-mediated pathways and on cardiac glucose and ketone metabolism in the failing heart. We focus on empagliflozin as it is the gliflozin with the most abundant experimental evidence for direct effects on the heart. Where useful, we aim to compare empagliflozin to other gliflozins. To facilitate understanding of empagliflozin-induced alterations, we first give a short summary of the pathophysiological role of CaMKII in heart failure, as well as cardiac changes of glucose and ketone body metabolism in the failing heart.
恩格列净是一种选择性钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，在 EMPA-REG-OUTCOME 试验（Zinman 等人，2015 年）中已显示可降低糖尿病患者的死亡率和心力衰竭住院率。令人惊讶的是，另一种 SGLT2 抑制剂达格列净即使在没有糖尿病的情况下也能对临床终点产生类似的影响（DAPA-HF 试验）（McMurray 等人，2019 年）。有许多潜在的机制，从改善血糖控制和血流动力学效应到改变心肌代谢、炎症、神经激素激活和细胞内离子稳态。在这里，我们回顾了格列净对心脏机电耦联的影响，重点介绍了新型 CaMKII 介导的途径以及心力衰竭中心脏葡萄糖和酮体代谢。我们专注于恩格列净，因为它是最有丰富实验证据表明对心脏有直接作用的格列净。在有用的地方，我们旨在将恩格列净与其他格列净进行比较。为了便于理解恩格列净引起的变化，我们首先简要总结 CaMKII 在心力衰竭中的病理生理作用，以及心力衰竭中心脏葡萄糖和酮体代谢的变化。
