Rosuvastatin effects on the HDL proteome in hyperlipidemic patients
Author:
Vavlukis Ana1ORCID, Mladenovska Kristina1ORCID, Davalieva Katarina2ORCID, Vavlukis Marija3ORCID, Dimovski Aleksandar12ORCID
Affiliation:
1. University Ss Cyril and Methodius Faculty of Pharmacy , Skopje RN Macedonia 2. Macedonian Academy of Sciences and Arts, Research Center for Genetic Engineering and Biotechnology „Georgi D. Efremov“ , Skopje RN Macedonia 3. University Ss Cyril and Methodius Faculty of Medicine , Skopje RN Macedonia
Abstract
AbstractThe advancements in proteomics have provided a better understanding of the functionality of apolipoproteins and lipoprotein-associated proteins, with the HDL lipoprotein fraction being the most studied. The focus of this study was to evaluate the HDL proteome in dyslipidemic subjects without an established cardiovascular disease, as well as to test whether rosuvastatin treatment alters the HDL proteome. Patients with primary hypercholesterolemia or mixed dyslipidemia were assigned to 20 mg/day rosuvastatin and blood samples were drawn at study entry and after 12 weeks of treatment. A label-free LC-MS/MS protein profiling was conducted, coupled with bioinformatics analysis. Sixty-nine HDL proteins were identified, belonging to four main biological function clusters: lipid transport and metabolism; platelet activation, degranulation, and aggregation, wound response and wound healing; immune response; inflammatory and acute phase response. Five HDL proteins showed statistically significant differences in the abundance (Anova ≤ 0.05), before and after rosuvastatin treatment. Platelet factor 4 variant (PF4V1), Pregnancy-specific beta-1-glycoprotein 2 (PSG2), Profilin-1 (PFN1) and Keratin type II cytoskeletal 2 epidermal (KRT2) showed decreased expressions, while Integrin alpha-IIb (ITGA2B) showed an increased expression after treatment with rosuvastatin. The ELISA validation of PFN1 segregated the subjects into responders and non-responders, as PFN1 levels after rosuvastatin were shown to mostly depend on the subjects’ inflammatory phenotype. Findings from this study introduce novel insights into the HDL proteome and statin pleiotropism.
Publisher
Walter de Gruyter GmbH
Subject
Pharmaceutical Science,Pharmacology,General Medicine
Reference44 articles.
1. F. L. J. Visseren, F. Mach, Y. M. Smulders, D. Carballo, K. C. Koskinas, M. Bäck, A. Benetos, A. Biffi, M. .J. Boavida, D. Capodanno, B. Cosyns, C. Crawford, C. H. Davos, I. Desormais, E. Di Angelan-tonio, O. Franco, S. Halvorsen, R. F. Hobbs, M. Hollander, E. Jankowska, M. Michal, S. Sacco, N. Sattar, L. Tokgozoglu, S. Tonstad, K. P Tsioufis, I. van Dis, I. van Gelder, C. Wanner and B. Williams, ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies with the special contribution of the European Association of Preventive Cardiology (EAPC), Eur. Heart J. 42(34) (2021) 3227-3337 2. F. L. J. Visseren, F. Mach, Y. M. Smulders, D. Carballo, K. C. Koskinas, M. Bäck, A. Benetos, A. Biffi, M. .J. Boavida, D. Capodanno, B. Cosyns, C. Crawford, C. H. Davos, I. Desormais, E. Di Angelan-tonio, O. Franco, S. Halvorsen, R. F. Hobbs, M. Hollander, E. Jankowska, M. Michal, S. Sacco, N. Sattar, L. Tokgozoglu, S. Tonstad, K. P Tsioufis, I. van Dis, I. van Gelder, C. Wanner and B. Williams, ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies with the special contribution of the European Association of Preventive Cardiology (EAPC), Eur. Heart J. 42 3. (34) (2021) 3227-3337; https://doi.org/10.1093/eurheartj/ehab484 4. F. Mach, C. Baigent, A. L. Catapano, K. C. Koskinas, M. Casula, L. Badimon, M. J. Chapman, G. G. De Backer, V. Delgado, I. M. Graham, A. Halliday, U. Landmesser, G. Riccardi, D. J. Richter, M. S. Sabatine, M. Taskinen, L. Tokgozoglu and O. Wiklund, ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS), European Heart Journal 41(1) (2020) 111-188 5. F. Mach, C. Baigent, A. L. Catapano, K. C. Koskinas, M. Casula, L. Badimon, M. J. Chapman, G. G. De Backer, V. Delgado, I. M. Graham, A. Halliday, U. Landmesser, G. Riccardi, D. J. Richter, M. S. Sabatine, M. Taskinen, L. Tokgozoglu and O. Wiklund, ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS), European Heart Journal 41
|
|