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

• Published in: Frontiers in cardiovascular medicine Vol. 11; p. 1417044
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18-07-2024
• Subjects: anti-PCSK9; atherosclerosis; Cardiovascular Medicine; dyslipidemia; hypercholesterolemia; inflammatory cytokines; LDL cholesterol; anti-PCSK9; atherosclerosis; statin resistance; inflammatory cytokines; LDL cholesterol; dyslipidemia; hypercholesterolemia
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2024.1417044

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 anti-inflammatory mediators depending on the clinical setting.
To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH.
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.
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 anti-atherogenic effects, indicating potential benefits for clinical outcomes.