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

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  • dc.contributor.author Rehues, Pere
  • dc.contributor.author Girona, Josefa
  • dc.contributor.author Guardiola, Montse
  • dc.contributor.author Plana, Nuria
  • dc.contributor.author Scicali, Roberto
  • dc.contributor.author Piro, Salvatore
  • dc.contributor.author Muñiz-Grijalvo, Ovidio
  • dc.contributor.author Díaz Díaz, José Luis
  • dc.contributor.author Recasens, Lluís
  • dc.contributor.author Pinyol, Marta
  • dc.contributor.author Rosales, Roser
  • dc.contributor.author Esteban, Yaiza
  • dc.contributor.author Amigó, Núria
  • dc.contributor.author Masana, Luís
  • dc.contributor.author Ibarretxe, Daiana
  • dc.contributor.author Ribalta, Josep
  • dc.date.accessioned 2024-04-17T06:20:33Z
  • dc.date.available 2024-04-17T06:20:33Z
  • dc.date.issued 2023
  • dc.description.abstract 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Rehues P, Girona J, Guardiola M, Plana N, Scicali R, Piro S, et al. 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. Int J Mol Sci. 2023 Jan 24;24(3):2319. DOI: 10.3390/ijms24032319
  • dc.identifier.doi http://dx.doi.org/10.3390/ijms24032319
  • dc.identifier.issn 1422-0067
  • dc.identifier.uri http://hdl.handle.net/10230/59802
  • dc.language.iso eng
  • dc.publisher MDPI
  • dc.relation.ispartof Int J Mol Sci. 2023 Jan 24;24(3):2319
  • dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword PCSK9
  • dc.subject.keyword Alirocumab
  • dc.subject.keyword Glycoproteins
  • dc.subject.keyword Apolipoprotein C-III
  • dc.subject.keyword Inflammation
  • dc.subject.keyword LDL
  • dc.title 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
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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