Karakasis Paschalis, Patoulias Dimitrios, Theofilis Panagiotis, Pamporis Konstantinos, Sagris Marios, Vlachakis Panayotis K, Koufakis Theocharis, Antoniadis Antonios P, Fragakis Nikolaos
Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece.
Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54124 Thessaloniki, Greece.
Int J Mol Sci. 2025 Mar 26;26(7):3050. doi: 10.3390/ijms26073050.
Coronary microvascular dysfunction (CMD) is a key contributor to myocardial ischemia and adverse cardiovascular outcomes, particularly in individuals with metabolic disorders such as type 2 diabetes (T2D). While conventional therapies primarily target epicardial coronary disease, effective treatments for CMD remain limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as promising agents with cardiovascular benefits extending beyond glycemic control. Preclinical and clinical evidence suggests that GLP-1R activation enhances coronary microvascular function through mechanisms including improved endothelial function, increased nitric oxide bioavailability, attenuation of oxidative stress, and reduced vascular inflammation. Moreover, GLP-1R agonists have been shown to improve myocardial blood flow, myocardial perfusion reserve, and coronary endothelial function, particularly in high-risk populations. Despite these promising findings, inconsistencies remain across studies due to variability in patient populations, study designs, and imaging methodologies. This review summarizes current evidence on the role of GLP-1R agonists in myocardial perfusion, bridging mechanistic insights with clinical outcomes. Further large-scale, well-designed trials are needed to clarify their long-term impact on coronary microcirculation and explore their potential as targeted therapies for CMD.
冠状动脉微血管功能障碍（CMD）是心肌缺血和不良心血管结局的关键促成因素，尤其是在患有2型糖尿病（T2D）等代谢紊乱的个体中。虽然传统疗法主要针对心外膜冠状动脉疾病，但针对CMD的有效治疗方法仍然有限。胰高血糖素样肽-1受体（GLP-1R）激动剂已成为有前景的药物，其心血管益处超出了血糖控制范围。临床前和临床证据表明，GLP-1R激活通过改善内皮功能、增加一氧化氮生物利用度、减轻氧化应激和减少血管炎症等机制增强冠状动脉微血管功能。此外，GLP-1R激动剂已被证明可改善心肌血流、心肌灌注储备和冠状动脉内皮功能，尤其是在高危人群中。尽管有这些有前景的发现，但由于患者人群、研究设计和成像方法的差异，各研究之间仍存在不一致之处。本综述总结了关于GLP-1R激动剂在心肌灌注中作用的当前证据，将机制见解与临床结果联系起来。需要进一步的大规模、精心设计的试验来阐明它们对冠状动脉微循环的长期影响，并探索它们作为CMD靶向治疗的潜力。
