Rosuvastatin effects on the HDL proteome in hyperlipidemic patients
The 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 esta...
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Sciendo
2023-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2023-0034 |
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| author | Vavlukis Ana Mladenovska Kristina Davalieva Katarina Vavlukis Marija Dimovski Aleksandar |
| author_facet | Vavlukis Ana Mladenovska Kristina Davalieva Katarina Vavlukis Marija Dimovski Aleksandar |
| author_sort | Vavlukis Ana |
| collection | DOAJ |
| description | The 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. |
| format | Article |
| id | doaj-art-ac5e79b0514541b68efb42071adda702 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2023-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-ac5e79b0514541b68efb42071adda7022025-02-03T05:22:44ZengSciendoActa Pharmaceutica1846-95582023-09-0173336338410.2478/acph-2023-0034Rosuvastatin effects on the HDL proteome in hyperlipidemic patientsVavlukis Ana0Mladenovska Kristina1Davalieva Katarina2Vavlukis Marija3Dimovski Aleksandar4University Ss Cyril and Methodius Faculty of Pharmacy, 1000SkopjeRN MacedoniaUniversity Ss Cyril and Methodius Faculty of Pharmacy, 1000SkopjeRN MacedoniaMacedonian Academy of Sciences and Arts, Research Center for Genetic Engineering and Biotechnology „Georgi D. Efremov“, 1000SkopjeRN MacedoniaUniversity Ss Cyril and Methodius Faculty of Medicine, 1000SkopjeRN MacedoniaUniversity Ss Cyril and Methodius Faculty of Pharmacy, 1000SkopjeRN MacedoniaThe 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.https://doi.org/10.2478/acph-2023-0034proteomicshigh-density lipoproteinrosuvastatinprofilin-1phospholipid transfer proteinplatelet factor 4 variant |
| spellingShingle | Vavlukis Ana Mladenovska Kristina Davalieva Katarina Vavlukis Marija Dimovski Aleksandar Rosuvastatin effects on the HDL proteome in hyperlipidemic patients Acta Pharmaceutica proteomics high-density lipoprotein rosuvastatin profilin-1 phospholipid transfer protein platelet factor 4 variant |
| title | Rosuvastatin effects on the HDL proteome in hyperlipidemic patients |
| title_full | Rosuvastatin effects on the HDL proteome in hyperlipidemic patients |
| title_fullStr | Rosuvastatin effects on the HDL proteome in hyperlipidemic patients |
| title_full_unstemmed | Rosuvastatin effects on the HDL proteome in hyperlipidemic patients |
| title_short | Rosuvastatin effects on the HDL proteome in hyperlipidemic patients |
| title_sort | rosuvastatin effects on the hdl proteome in hyperlipidemic patients |
| topic | proteomics high-density lipoprotein rosuvastatin profilin-1 phospholipid transfer protein platelet factor 4 variant |
| url | https://doi.org/10.2478/acph-2023-0034 |
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