{"id":"2b3a191ee8aa","type":"article","url":"https://hartvaat.nl/2026/09/29/lox-1-nlrp3-as-verklaart-residuair-inflammatoir-risico-bij-atherosclerose/","title":"LOX-1-NLRP3-as verklaart residuair inflammatoir risico bij atherosclerose","title_en":"An Update of Oxidative Stress in Atherosclerosis with Emphasis on the LOX-1-NLRP3 Inflammasome Axis.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","internist"],"tags":[],"journal":"Current atherosclerosis reports","doi":"10.1007/s11883-026-01462-8","source_url":"https://doi.org/10.1007/s11883-026-01462-8","authors":["Keshav Garg","Nitesh Gautam","Ankit Agrawal","Jawahar L Mehta"],"significance":5,"published":"2026-10-06","source_date":"2026-09-29","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/","https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/"],"congress":"","summary_en":"This narrative review examines oxidative stress and the LOX-1-NLRP3 inflammasome axis as key drivers of residual inflammatory risk in atherosclerosis, particularly in patients already on optimal lipid-lowering therapy. Mechanistic insights reveal how LOX-1 activation amplifies mitochondrial damage and IL-1β release, providing a biological rationale for the clinical success of anti-inflammatory trials (CANTOS, COLCOT, LoDoCo2) and the recent FDA approval of colchicine for secondary prevention. For clinicians, this framework clarifies why vascular inflammation persists despite LDL-C targets and highlights emerging therapeutic avenues, including NLRP3 inhibitors and biomarker-guided combination strategies.","created":"2026-09-30T01:06:58Z","updated":"2026-09-30T01:06:58Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Deze overzichtsstudie beschrijft de rol van oxidatieve stress en de LOX-1-NLRP3-inflammasoom-as als centrale drijvers van residuair inflammatoir risico bij atherosclerose-patiënten, zelfs bij optimale LDL-C-daling. Mechanistische inzichten tonen aan hoe LOX-1-activatie mitochondriale schade en IL-1β-vrijgave versterkt, wat de klinische validatie van de inflammatoire hypothese (CANTOS, COLCOT, LoDoCo2) en de FDA-goedkeuring van colchicine verklaart. Voor de praktijk biedt dit een helder kader waarom patiënten ondanks statinen en PCSK9-remmers toch een verhoogd risico houden, en wijst het de weg naar toekomstige strategieën zoals NLRP3-remmers en biomarker-gestuurde combinatietherapie.","abstract_original":"PURPOSE OF REVIEW: Atherosclerosis is a chronic inflammatory disease in which oxidative stress serves as a final common mechanism linking endothelial injury, lipoprotein oxidation, immune activation, and plaque progression. Since the original description of reactive oxygen species (ROS) generating and antioxidant systems in atherogenesis, substantial advances have reshaped the mechanistic and therapeutic landscape. This review provides a comprehensive update on oxidative stress in atherosclerosis, with particular emphasis on the LOX-1-NLRP3 inflammasome axis as a central driver of residual inflammatory risk. RECENT FINDINGS: The lectin-like oxidized LDL receptor-1 (LOX-1) has been established as a regulated, druggable node through the identification of TRIM31-mediated ubiquitination. The first-in-human LOX-1 antibody trial (GOLDILOX-TIMI 69) demonstrated near-complete soluble LOX-1 suppression and IL-6 reduction, though plaque regression was not achieved. The mechanistic cascade linking LOX-1 activation to mitochondrial DNA damage, impaired autophagy, and NLRP3 inflammasome-driven IL-1β release now provides a molecular explanation for persistent vascular inflammation even when LDL-C targets are met with high-intensity statins and PCSK9 inhibitors. Clinical validation of the inflammation hypothesis through CANTOS, COLCOT, and LoDoCo2 has led to FDA approval of colchicine for secondary cardiovascular prevention. Emerging evidence implicates clonal hematopoiesis, vascular senescence, and the senescence-associated secretory phenotype as amplifiers of oxidative-inflammatory signaling in the vessel wall. The LOX-1-NLRP3 axis represents an important mechanistic advance since the original characterization of oxidative stress in atherosclerosis. Future strategies, including direct NLRP3 inhibitors, longer-duration LOX-1 antibody trials, biomarker-guided combination therapy, and mitochondria-targeted antioxidants, aim to close the residual inflammatory risk gap that persists despite optimal lipid-lowering therapy."}