Articles producció científica> Medicina i Cirurgia

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

  • Identification data

    Identifier: imarina:9292114
    Authors:
    Rehues, PGirona, JGuardiola, MPlana, NScicali, RPiro, SMuñiz-Grijalvo, ODíaz-Díaz, JLRecasens, LPinyol, MRosales, REsteban, YAmigó, NMasana, LIbarretxe, DRibalta, J
    Abstract:
    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 (
  • Others:

    Author, as appears in the article.: Rehues, P; Girona, J; Guardiola, M; Plana, N; Scicali, R; Piro, S; Muñiz-Grijalvo, O; Díaz-Díaz, JL; Recasens, L; Pinyol, M; Rosales, R; Esteban, Y; Amigó, N; Masana, L; Ibarretxe, D; Ribalta, J
    Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
    URV's Author/s: Girona Tell, Josefa / Guardiola Guionnet, Montserrat / Ibarretxe Gerediaga, Daiana / Masana Marín, Luis / Plana Gil, Núria / Rehues Masip, Pere / Ribalta Vives, Josep / ROSALES RIBAS, ROSER
    Keywords: Pcsk9 Of-function mutations Ldl Inflammation Glycoproteins Apolipoprotein c-iii Alirocumab triglycerides reactive protein plasma lipoproteins ldl-cholesterol ldl inflammatory response inflammation glycoproteins glyca evolocumab apolipoprotein c-iii alirocumab
    Abstract: 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.
    Thematic Areas: 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
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: daiana.ibarretxe@urv.cat luis.masana@urv.cat pere.rehues@urv.cat josefa.girona@urv.cat pere.rehues@urv.cat josefa.girona@urv.cat montse.guardiola@urv.cat josep.ribalta@urv.cat
    Author identifier: 0000-0002-0789-4954 0000-0002-6267-8779 0000-0002-6267-8779 0000-0002-9696-7384 0000-0002-8879-4719
    Record's date: 2024-08-03
    Papper version: info:eu-repo/semantics/publishedVersion
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: International Journal Of Molecular Sciences. 24 (3):
    APA: Rehues, P; Girona, J; Guardiola, M; Plana, N; Scicali, R; Piro, S; Muñiz-Grijalvo, O; Díaz-Díaz, JL; Recasens, L; Pinyol, M; Rosales, R; Esteban, Y; A (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), -. DOI: 10.3390/ijms24032319
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry & Molecular Biology,Catalysis,Chemistry, Multidisciplinary,Computer Science Applications,Inorganic Chemistry,Medicine (Miscellaneous),Molecular Biology,Organic Chemistry,Physical and Theoretical Chemistry,Spectroscopy
    Pcsk9
    Of-function mutations
    Ldl
    Inflammation
    Glycoproteins
    Apolipoprotein c-iii
    Alirocumab
    triglycerides
    reactive protein
    plasma
    lipoproteins
    ldl-cholesterol
    ldl
    inflammatory response
    inflammation
    glycoproteins
    glyca
    evolocumab
    apolipoprotein c-iii
    alirocumab
    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
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