Caldarelli Mario, Franza Laura, Cutrupi Sebastiano, Menegolo Martina, Franceschi Francesco, Gasbarrini Antonio, Gambassi Giovanni, Cianci Rossella
Department of Medical and Surgical Sciences, Catholic University of Sacred Heart, 00168 Rome, Italy.
Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy.
Int J Mol Sci. 2025 Jun 6;26(12):5439. doi: 10.3390/ijms26125439.
Chronic inflammation is an important contributor to the development of cardiovascular disorders, and inflammasomes, especially the NOD-like receptor protein 3 (NLRP3), are emerging as crucial mediators in this context. Inflammasomes are activated through receptor-mediated danger signals, such as cholesterol crystals and cellular damage products, thereby stimulating the secretion of pro-inflammatory cytokines, which sustains inflammation. This mechanism drives atherosclerosis (via plaque formation and destabilization), heart failure (via fibrotic remodeling), and pericarditis (via exacerbation of pericardial inflammation). Therapeutic approaches seek to block inflammasome activation or their pro-inflammatory pathways. Colchicine, interleukin-1 inhibitors (anakinra, canakinumab), and Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors have a positive impact on cardiovascular inflammation. Various new compounds, such as MCC950, have been described as novel specific inhibitors of NLRP3. Further studies are needed to validate the effectiveness and safety of these treatments. Further elucidating the role of inflammasomes in cardiovascular disease could open the way to achieving more effective therapies, allowing for better management of high-risk cardiovascular patients.
慢性炎症是心血管疾病发生发展的重要因素,而炎性小体,尤其是NOD样受体蛋白3(NLRP3),正成为这一过程中的关键介质。炎性小体通过受体介导的危险信号(如胆固醇晶体和细胞损伤产物)被激活,从而刺激促炎细胞因子的分泌,维持炎症反应。这一机制导致动脉粥样硬化(通过斑块形成和不稳定)、心力衰竭(通过纤维化重塑)和心包炎(通过心包炎症加剧)。治疗方法旨在阻断炎性小体的激活或其促炎途径。秋水仙碱、白细胞介素-1抑制剂(阿那白滞素、卡那单抗)和钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂对心血管炎症有积极影响。各种新化合物,如MCC950,已被描述为NLRP3的新型特异性抑制剂。需要进一步研究来验证这些治疗方法的有效性和安全性。进一步阐明炎性小体在心血管疾病中的作用可能为实现更有效的治疗开辟道路,从而更好地管理心血管高危患者。