Piperis Christos, Marathonitis Anastasios, Anastasiou Artemis, Theofilis Panagiotis, Mourouzis Konstantinos, Giannakodimos Alexios, Tryfou Elsi, Oikonomou Evangelos, Siasos Gerasimos, Tousoulis Dimitris
3rd Department of Cardiology, Thoracic Diseases General Hospital "Sotiria", National and Kapodistrian University of Athens, 11527 Athens, Greece.
1st Department of Cardiology, "Hippokration" General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Biomedicines. 2024 Oct 11;12(10):2314. doi: 10.3390/biomedicines12102314.
Heart failure (HF) is a growing concern due to the aging population and increasing prevalence of comorbidities. Despite advances in treatment, HF remains a significant burden, necessitating novel therapeutic approaches. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have emerged as a promising treatment option, demonstrating benefits across the entire spectrum of HF, regardless of left ventricular ejection fraction (LVEF). This review explores the multifaceted mechanisms through which SGLT2is exert cardioprotective effects, including modulation of energy metabolism, reduction of oxidative stress, attenuation of inflammation, and promotion of autophagy. SGLT2is shift myocardial energy substrate utilization from carbohydrates to more efficient fatty acids and ketone bodies, enhancing mitochondrial function and reducing insulin resistance. These inhibitors also mitigate oxidative stress by improving mitochondrial biogenesis, reducing reactive oxygen species (ROS) production, and regulating calcium-signaling pathways. Inflammation, a key driver of HF progression, is alleviated through the suppression of proinflammatory cytokines and modulation of immune cell activity. Additionally, SGLT2is promote autophagy, facilitating the clearance of damaged cellular components and preserving myocardial structure and function Beyond their glucose-lowering effects, SGLT2is provide significant benefits in patients with chronic kidney disease (CKD) and HF, reducing the progression of CKD and improving overall survival. The pleiotropic actions of SGLT2is highlight their potential as a cornerstone in HF management. Further research is needed to fully elucidate their mechanisms and optimize their use in clinical practice.
由于人口老龄化和合并症患病率上升，心力衰竭（HF）日益受到关注。尽管治疗方面取得了进展，但HF仍然是一个重大负担，需要新的治疗方法。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）已成为一种有前景的治疗选择，无论左心室射血分数（LVEF）如何，在整个HF范围内均显示出益处。本综述探讨了SGLT2i发挥心脏保护作用的多方面机制，包括调节能量代谢、减少氧化应激、减轻炎症和促进自噬。SGLT2i将心肌能量底物利用从碳水化合物转变为更有效的脂肪酸和酮体，增强线粒体功能并降低胰岛素抵抗。这些抑制剂还通过改善线粒体生物发生、减少活性氧（ROS）产生和调节钙信号通路来减轻氧化应激。炎症是HF进展的关键驱动因素，通过抑制促炎细胞因子和调节免疫细胞活性得以减轻。此外，SGLT2i促进自噬，有助于清除受损的细胞成分并维持心肌结构和功能。除了其降糖作用外，SGLT2i在慢性肾脏病（CKD）和HF患者中具有显著益处，可减缓CKD进展并改善总体生存率。SGLT2i的多效性作用凸显了它们作为HF管理基石的潜力。需要进一步研究以充分阐明其机制并优化其在临床实践中的应用。
