PCSK9 Inhibitors Have Apolipoprotein C-III-Related Anti-Inflammatory Activity, Assessed by 1H-NMR Glycoprotein Profile in Subjects at High or very High Cardiovascular Risk

Autor según el artículo: Rehues, Pere; Girona, Josefa; Guardiola, Montse; Plana, Nuria; Scicali, Roberto; Piro, Salvatore; Muniz-Grijalvo, Ovidio; Diaz-Diaz, Jose Luis; Recasens, Lluis; Pinyol, Marta; Rosales, Roser; Esteban, Yaiza; Amigo, Nuria; Masana, Lluis; Ibarretxe, Daiana; Ribalta, Josep

Departamento: Medicina i Cirurgia; Ciències Mèdiques Bàsiques

Autor/es de la URV: Girona Tell, Josefa / Guardiola Guionnet, Montserrat / Ibarretxe Gerediaga, Daiana / Masana Marín, Luis / Plana Gil, Núria / Rehues Masip, Pere / Ribalta Vives, Josep / ROSALES RIBAS, ROSER

Palabras clave: Triglycerides; Risk factors; Proton magnetic resonance spectroscopy; Proprotein convertase 9; Pcsk9 protein, human; Pcsk9 inhibitors; Pcsk9; Of-function mutations; Magnetic resonance spectroscopy; Lipoproteins; Ldl; Inflammation; Humans; Heart disease risk factors; Glycoproteins; Cholesterol, ldl; Cholesterol; Cardiovascular diseases; C-reactive protein; Apolipoprotein c-iii; Anti-inflammatory agents; Alirocumab; triglycerides; reactive protein; plasma; lipoproteins; ldl-cholesterol; ldl; inflammatory response; inflammation; glycoproteins; glyca; evolocumab; apolipoprotein c-iii; alirocumab

Resumen: Highlights: What are the main findings? PCSK9 inhibition significantly reduces 1H-NMR glycoprotein signals and does not affect hsCRP levels. Apolipoprotein C-III and triglycerides are also decreased by iPCSK9. The decrease in glycoproteins correlates with the decrease in apoC-III and TG. What is the implication of the main finding? PCSK9 inhibition significantly reduces inflammation Atherosclerosis is a chronic inflammatory disease caused by the accumulation of cholesterol in the intima. Proprotein convertase subtilisin/kexin type 9 inhibitors (iPCSK9) can reduce low-density lipoprotein (LDL) cholesterol levels by 60%, but there is still no evidence that they can lower markers of systemic inflammation such as high-sensitivity C-reactive protein (hsCRP). Acute-phase serum glycoproteins are upregulated in the liver during systemic inflammation, and their role as inflammatory biomarkers is under clinical evaluation. In this observational study, we evaluate the effects of iPCSK9 on glycoproteins (Glyc) A, B and F. Thirty-nine patients eligible for iPCSK9 therapy were enrolled. One sample before and after one to six months of iPCSK9 therapy with alirocumab was obtained from each patient. Lipids, apolipoproteins, hsCRP and PCSK9 levels were measured by biochemical analyses, and the lipoprotein and glycoprotein profiles were measured by 1H nuclear magnetic resonance (1H-NMR). The PCSK9 inhibitor reduced total (36.27%, p < 0.001), LDL (55.05%, p < 0.001) and non-high-density lipoprotein (HDL) (45.11%, p < 0.001) cholesterol, apolipoprotein (apo) C-III (10%, p < 0.001), triglycerides (9.92%, p < 0.001) and glycoprotein signals GlycA (11.97%, p < 0.001), GlycB (3.83%, p = 0.017) and GlycF (7.26%, p < 0.001). It also increased apoA-I (2.05%, p = 0.043) and HDL cholesterol levels (11.58%, p < 0.001). Circulating PCSK9 levels increased six-fold (626.28%, p < 0.001). The decrease in Glyc signals positively correlated with the decrease in triglycerides and apoC-III. In conclusion, in addition to LDL cholesterol, iPCSK9 therapy also induces a reduction in systemic inflammation measured by 1H-NMR glycoprotein signals, which correlates with a decrease in triglycerides and apoC-III.

Áreas temáticas: Zootecnia / recursos pesqueiros; Spectroscopy; Saúde coletiva; Química; Psicología; Physical and theoretical chemistry; Organic chemistry; Odontología; Nutrição; Molecular biology; Medicine (miscellaneous); Medicina veterinaria; Medicina iii; Medicina ii; Medicina i; Materiais; Interdisciplinar; Inorganic chemistry; Geociências; Farmacia; Engenharias iv; Engenharias ii; Engenharias i; Educação física; Computer science applications; Ciências biológicas iii; Ciências biológicas ii; Ciências biológicas i; Ciências ambientais; Ciências agrárias i; Ciência de alimentos; Ciência da computação; Chemistry, multidisciplinary; Catalysis; Biotecnología; Biodiversidade; Biochemistry & molecular biology; Astronomia / física

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

Direcció de correo del autor: pere.rehues@urv.cat; daiana.ibarretxe@urv.cat; josefa.girona@urv.cat; pere.rehues@urv.cat; josefa.girona@urv.cat; montse.guardiola@urv.cat; luis.masana@urv.cat; josep.ribalta@urv.cat

Fecha de alta del registro: 2025-02-19

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://www.mdpi.com/1422-0067/24/3/2319

URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: International Journal Of Molecular Sciences. 24 (3): 2319-

Referencia de l'ítem segons les normes APA: Rehues, Pere; Girona, Josefa; Guardiola, Montse; Plana, Nuria; Scicali, Roberto; Piro, Salvatore; Muniz-Grijalvo, Ovidio; Diaz-Diaz, Jose Luis; Recase (2023). PCSK9 Inhibitors Have Apolipoprotein C-III-Related Anti-Inflammatory Activity, Assessed by 1H-NMR Glycoprotein Profile in Subjects at High or very High Cardiovascular Risk. International Journal Of Molecular Sciences, 24(3), 2319-. DOI: 10.3390/ijms24032319

DOI del artículo: 10.3390/ijms24032319

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2023

Tipo de publicación: Journal Publications