Key result
Targeting the NLRP3 inflammasome shows cardiovascular promise but faces specificity and long-term safety challenges.
Targeting the NLRP3 inflammasome offers a promising approach for treating cardiovascular diseases by modulating chronic inflammation, though precision and safety remain key challenges.
NLRP3 inhibition should not yet change CVD practice; leaves open development of tissue-specific agents.
The NLRP3 inflammasome plays a pivotal role in innate immune responses and has emerged as an important contributor to the pathogenesis of cardiovascular diseases (CVDs), including atherosclerosis, heart failure, myocardial infarction, and hypertension-related organ damage. Upon activation, NLRP3 promotes the maturation and release of IL-1β and IL-18 and triggers pyroptosis, thereby exacerbating endothelial dysfunction, vascular smooth muscle cell proliferation and migration, lipid metabolic disorders, and adverse myocardial remodeling. These processes form a self-perpetuating cycle of inflammation and tissue injury. Therapeutic strategies targeting the NLRP3 pathway have progressed from non-specific anti-inflammatory agents, such as aspirin and colchicine, to more precise interventions that block NLRP3 oligomerization (e.g., MCC950 and its analogs), neutralize upstream cytokines, modulate metabolic and oxidative stress pathways, and employ advanced delivery systems including gene editing and nanocarriers. Despite these advances, current approaches are limited by insufficient target specificity, incomplete long-term safety data, and the absence of disease subtype-specific regimens. This review provides a comprehensive overview of multi-level therapeutic strategies directed against the NLRP3 inflammasome, critically evaluates preclinical and clinical evidence—including findings from the CANTOS trial—and discusses the translational potential of NLRP3-targeted immunometabolic therapy in CVDs. Looking forward, integration of multi-omics technologies, such as single-cell sequencing and spatial transcriptomics, with well-designed clinical studies will be essential to delineate the context-specific roles of NLRP3 across different CVD subtypes and to clarify its interactions with protective pathways such as AMPK and SIRT1. These efforts may facilitate the development of more selective, tissue-targeted, and safer therapeutic agents for the precision management of cardiovascular diseases.
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Zhang et al. (2026) conducted a review in Cardiovascular diseases. NLRP3 inflammasome targeted therapies was evaluated. Targeting the NLRP3 inflammasome presents a promising therapeutic strategy for cardiovascular diseases, though current interventions face challenges regarding target specificity and long-term safety.
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