Muhs Tillmann, Ljubojevic-Holzer Senka, Sattler Susanne
Department of Pharmacology, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria.
Department of Cardiology, LKH Univ. Klinikum Graz, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Curr Cardiol Rep. 2025 Feb 19;27(1):57. doi: 10.1007/s11886-025-02211-0.
PURPOSE OF REVIEW: The inclusion of immunomodulatory strategies as supportive therapies in ischemic heart disease (IHD) has garnered significant support over recent years. Several such approaches appear to be unified through their ultimate target, the NLRP3 inflammasome. This review presents a brief update on immunomodulatory strategies in the continuum of conditions constituting ischemic heart disease and emphasising on the seemingly unifying mechanism of NLRP3 activation as well as modulation across these conditions. RECENT FINDINGS: The NLRP3 inflammasome is a multiprotein complex assembled upon inflammatory stimulation, causing the release of pro-inflammatory cytokines and initiating pyroptosis. The NLRP3 pathway is relevant in inflammatory signalling of cardiac immune cells as well as non-immune cells in the myocardium, including cardiomyocytes, fibroblasts and endothelial cells. In addition to a focus on clinical outcome and efficacy trials of targeting NLRP3-related pathways, the potential connection between immunomodulation in cardiology and the NLRP3 pathway is currently being explored in preclinical trials. Colchicine, cytokine-based approaches and SGLT2 inhibitors have emerged as promising agents. However, the conditions comprising IHD including atherosclerosis, coronary artery disease (CAD), myocardial infarction (MI) and ischemic cardiomyopathy/heart failure (iCMP/HF) are not equally amenable to immunomodulation with the respective drugs. Atherosclerosis, coronary artery disease and ischemic cardiomyopathy are affected by chronic inflammation, but the immunomodulatory approach to acute inflammation in the post-MI setting remains a pharmacological challenge, as detrimental and regenerative effects of myocardial inflammation are initiated in unison. The NLRP3 inflammasome lies at the center of cell mediated inflammation in IHD. Recent trial evidence has highlighted anti-inflammatory effects of colchicine, interleukin-based therapy as well as SGLT2i in IHD and that the respective drugs modulate the NLRP3 inflammasome.
综述目的：近年来，免疫调节策略作为缺血性心脏病（IHD）的支持性治疗方法已获得广泛支持。其中几种方法似乎通过其最终靶点NLRP3炎性小体而统一起来。本综述简要介绍了构成缺血性心脏病的一系列病症中的免疫调节策略，并着重阐述了NLRP3激活以及在这些病症中调节的看似统一的机制。 最新发现：NLRP3炎性小体是一种在炎症刺激下组装的多蛋白复合物，可导致促炎细胞因子的释放并引发细胞焦亡。NLRP3途径与心脏免疫细胞以及心肌中的非免疫细胞（包括心肌细胞、成纤维细胞和内皮细胞）的炎症信号传导有关。除了关注靶向NLRP3相关途径的临床结果和疗效试验外，目前正在临床前试验中探索心脏病学中的免疫调节与NLRP3途径之间的潜在联系。秋水仙碱、基于细胞因子的方法和SGLT2抑制剂已成为有前景的药物。然而，构成IHD的病症，包括动脉粥样硬化、冠状动脉疾病（CAD）、心肌梗死（MI）和缺血性心肌病/心力衰竭（iCMP/HF），对各自药物的免疫调节作用并不相同。动脉粥样硬化、冠状动脉疾病和缺血性心肌病受慢性炎症影响，但心肌梗死后急性炎症的免疫调节方法仍然是一个药理学挑战，因为心肌炎症的有害和再生作用是同时启动的。NLRP3炎性小体处于IHD细胞介导炎症的中心。最近的试验证据突出了秋水仙碱、基于白细胞介素的疗法以及SGLT2i在IHD中的抗炎作用，并且各自的药物可调节NLRP3炎性小体。
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