AUTHOR=Morales-Portano Julieta Danira , Trujillo-Cortés Rafael , Roa-Martínez Bricia Margarita , Pérez-Cabeza de Vaca Rebeca , García Silvia , Mondragón-Terán Paul , Suárez-Cuenca Juan A. 

TITLE=Expression of pro- and anti-inflammatory cytokines during anti-proprotein convertase subtilisin/kexin type 9 therapy in patients with statin-resistant familial hypercholesterolemia

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1417044

DOI=10.3389/fcvm.2024.1417044

ISSN=2297-055X

ABSTRACT=Background: Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro-and antiinflammatory mediators depending on the clinical setting.To evaluate the effect of PCSK9i treatment on pro-and anti-inflammatory cytokines in patients with SR-FH.Methods: Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1-and M2-macrophages and monocytes.Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification.Results: Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1-and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers.PCSK9i therapy exerted subclinical anti-inflammatory and antiatherogenic effects, indicating potential benefits for clinical outcomes.