SGLT2 inhibitors and cardiac fibrosis: A comprehensive review.

IF 3.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Current Problems in Cardiology Pub Date : 2025-10-01 Epub Date: 2025-08-05 DOI:10.1016/j.cpcardiol.2025.103149
Paschalis Karakasis, Panagiotis Theofilis, Panayotis K Vlachakis, Anastasios Apostolos, Nikias Milaras, Nikolaos Ktenopoulos, Konstantinos Grigoriou, Aleksandra Klisic, Efstratios Karagiannidis, Barbara Fyntanidou, Dimitrios Patoulias, Antonios P Antoniadis, Nikolaos Fragakis
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引用次数: 0

Abstract

Cardiac fibrosis is a key pathological substrate that drives diastolic dysfunction, arrhythmogenesis, and heart failure progression across a spectrum of cardiometabolic disorders. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glucose lowering, have demonstrated pleiotropic effects on myocardial structure, notably attenuating fibrotic remodeling. Experimental models of diabetes, hypertension, ischemia, and cardiotoxicity consistently show that SGLT2 inhibitors mitigate interstitial and perivascular fibrosis through modulation of oxidative stress, mitochondrial function, autophagy, and canonical profibrotic signaling cascades, including TGF-β/Smad, STAT3, and mTOR. These actions are largely preserved in non-diabetic settings and appear to extend beyond hemodynamic or glycemic benefits. Clinical data, including cardiac magnetic resonance-based assessments, support the notion of diffuse fibrosis regression, particularly in heart failure with preserved ejection fraction and diabetic cardiomyopathy. Moreover, reductions in serum collagen biomarkers and improvements in myocardial energetics further substantiate their antifibrotic capacity. Nonetheless, fibrosis-specific endpoints remain underrepresented in major cardiovascular outcome trials, and histological validation in human tissue is lacking. Integrating artificial intelligence-driven fibrosis quantification, spatial transcriptomics, and high-resolution imaging may refine phenotyping and enable precision antifibrotic therapy. Whether fibrosis regression translates into durable clinical benefit remains an open question. This review comprehensively synthesizes the mechanistic, translational, and clinical evidence supporting the role of SGLT2 inhibitors as modulators of cardiac fibrosis across diverse cardiovascular disease states.

SGLT2抑制剂与心脏纤维化:全面回顾。
心脏纤维化是一个关键的病理底物,驱动舒张功能障碍,心律失常,心衰进展在一系列心脏代谢紊乱。钠-葡萄糖共转运蛋白2 (SGLT2)抑制剂,最初是为降血糖而开发的,已经证明对心肌结构有多效作用,特别是减轻纤维化重塑。糖尿病、高血压、缺血和心脏毒性的实验模型一致表明,SGLT2抑制剂通过调节氧化应激、线粒体功能、自噬和典型的促纤维化信号级联反应(包括TGF-β/Smad、STAT3和mTOR)来减轻间质和血管周围纤维化。这些作用在非糖尿病患者中很大程度上保留下来,并且似乎超出了血液动力学或血糖的益处。临床数据,包括基于心脏磁共振的评估,支持弥漫性纤维化消退的概念,特别是在保留射血分数的心力衰竭和糖尿病性心肌病中。此外,血清胶原生物标志物的减少和心肌能量的改善进一步证实了它们的抗纤维化能力。尽管如此,在主要的心血管结局试验中,纤维化特异性终点的代表性仍然不足,并且缺乏对人体组织的组织学验证。整合人工智能驱动的纤维化量化,空间转录组学和高分辨率成像可以改进表型并实现精确的抗纤维化治疗。纤维化消退是否转化为持久的临床益处仍然是一个悬而未决的问题。这篇综述全面综合了支持SGLT2抑制剂在不同心血管疾病状态下作为心脏纤维化调节剂作用的机制、转化和临床证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Problems in Cardiology
Current Problems in Cardiology 医学-心血管系统
CiteScore
4.80
自引率
2.40%
发文量
392
审稿时长
6 days
期刊介绍: Under the editorial leadership of noted cardiologist Dr. Hector O. Ventura, Current Problems in Cardiology provides focused, comprehensive coverage of important clinical topics in cardiology. Each monthly issues, addresses a selected clinical problem or condition, including pathophysiology, invasive and noninvasive diagnosis, drug therapy, surgical management, and rehabilitation; or explores the clinical applications of a diagnostic modality or a particular category of drugs. Critical commentary from the distinguished editorial board accompanies each monograph, providing readers with additional insights. An extensive bibliography in each issue saves hours of library research.
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