A sex-dependent role of Kv1.3 channels from macrophages in metabolic syndrome

• DOI: 10.3389/fphys.2024.1487775
• Publication Date: 2024-11-13T11:39:44Z
• Authors: Diego A. Peraza; Lucía Benito-Sala...; Sara Moreno-Estar; Esperanza Alonso; José R. López-López; M. Teresa Pérez-G...; Pilar Cidad
• Keywords: CD36; Endothelial Dysfunction

Introduction Coronary artery disease (CAD) is the foremost single cause of mortality and disability globally. Patients with type 2 diabetes (T2DM) have a higher incidence CAD, poorer prognosis. The low-grade inflammation associated to T2DM contributes increased morbidity worst outcomes after revascularization. Inflammatory signaling in vasculature supports endothelial dysfunction, leukocyte infiltration, macrophage activation metabolic (MMe) specific phenotype, which could contribute disorders ascular damage T2DM. We previously found that K v 1.3 blockers inhibit development intimal hyperplasia, thereby preventing restenosis. This inhibition was enhanced mouse model T2DM, where systemic administration also improve dysfunction by acting on unidentified cellular targets other than vascular smooth muscle. Here we characterize MMe phenotype our focus channels, explore their contribution potential role as ameliorate risk. Methods Results Male female BPH mice fed high-fat diet (HFD) develop syndrome (MetS) mRNA levels several + channels (K V 1.3, Ca 3.1, ir 2.1) markers (TNFα, NOS2, CD36) were analyzed. CD36 expression. Channel-specific fingerprinting highlights gender-specific increase fold change LPS stimulated macrophages from HFD compared standard (SD). functional expression significantly stimulation SD. Functional studies showed macrophage's did not phagocytosis or profile but relevant cell migration rate. Conclusion Altogether, data suggest inhibiting Kv1.3 disrupt vicious cycle insulin resistance, offering novel approach prevent MetS, its cardiovascular complications females.