Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33
One of the contributors to atherogenesis is enzymatically modified LDL (eLDL). eLDL was detected in all stages of aortic valve sclerosis and was demonstrated to trigger the activation of p38 mitogen-activated protein kinase (p38 MAPK), which has been identified as a pro-inflammatory protein in ather...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/7/1091 |
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| author | Annemarie Witz Denise Effertz Nora Goebel Matthias Schwab Ulrich F. W. Franke Michael Torzewski |
| author_facet | Annemarie Witz Denise Effertz Nora Goebel Matthias Schwab Ulrich F. W. Franke Michael Torzewski |
| author_sort | Annemarie Witz |
| collection | DOAJ |
| description | One of the contributors to atherogenesis is enzymatically modified LDL (eLDL). eLDL was detected in all stages of aortic valve sclerosis and was demonstrated to trigger the activation of p38 mitogen-activated protein kinase (p38 MAPK), which has been identified as a pro-inflammatory protein in atherosclerosis. In this study, we investigated the influence of eLDL on IL-6 and IL-33 induction, and also the impact of eLDL on calcification in aortic valve stenosis (AS). eLDL upregulated phosphate-induced calcification in valvular interstitial cells (VICs)/myofibroblasts isolated from diseased aortic valves, as demonstrated by alizarin red staining. Functional studies demonstrated activation of p38 MAPK as well as an altered gene expression of osteogenic genes known to be involved in vascular calcification. In parallel with the activation of p38 MAPK, eLDL also induced upregulation of the cytokines IL-6 and IL-33. The results suggest a pro-calcifying role of eLDL in AS via induction of IL-6 and IL-33. |
| first_indexed | 2024-03-11T01:15:50Z |
| format | Article |
| id | doaj.art-a31c4c644ff140a5844672bafe4f0244 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T01:15:50Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a31c4c644ff140a5844672bafe4f02442023-11-18T18:31:18ZengMDPI AGBiomolecules2218-273X2023-07-01137109110.3390/biom13071091Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33Annemarie Witz0Denise Effertz1Nora Goebel2Matthias Schwab3Ulrich F. W. Franke4Michael Torzewski5Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDepartment of Cardiovascular Surgery, Robert-Bosch-Hospital, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDepartment of Cardiovascular Surgery, Robert-Bosch-Hospital, 70376 Stuttgart, GermanyDepartment of Laboratory Medicine and Hospital Hygiene, Robert-Bosch-Hospital, 70376 Stuttgart, GermanyOne of the contributors to atherogenesis is enzymatically modified LDL (eLDL). eLDL was detected in all stages of aortic valve sclerosis and was demonstrated to trigger the activation of p38 mitogen-activated protein kinase (p38 MAPK), which has been identified as a pro-inflammatory protein in atherosclerosis. In this study, we investigated the influence of eLDL on IL-6 and IL-33 induction, and also the impact of eLDL on calcification in aortic valve stenosis (AS). eLDL upregulated phosphate-induced calcification in valvular interstitial cells (VICs)/myofibroblasts isolated from diseased aortic valves, as demonstrated by alizarin red staining. Functional studies demonstrated activation of p38 MAPK as well as an altered gene expression of osteogenic genes known to be involved in vascular calcification. In parallel with the activation of p38 MAPK, eLDL also induced upregulation of the cytokines IL-6 and IL-33. The results suggest a pro-calcifying role of eLDL in AS via induction of IL-6 and IL-33.https://www.mdpi.com/2218-273X/13/7/1091enzymatically modified LDL (eLDL)calcificationaortic valve stenosisVICs/myofibroblastsp38 MAPKIL-6 |
| spellingShingle | Annemarie Witz Denise Effertz Nora Goebel Matthias Schwab Ulrich F. W. Franke Michael Torzewski Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33 Biomolecules enzymatically modified LDL (eLDL) calcification aortic valve stenosis VICs/myofibroblasts p38 MAPK IL-6 |
| title | Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33 |
| title_full | Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33 |
| title_fullStr | Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33 |
| title_full_unstemmed | Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33 |
| title_short | Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33 |
| title_sort | pro calcifying role of enzymatically modified ldl eldl in aortic valve sclerosis via induction of il 6 and il 33 |
| topic | enzymatically modified LDL (eLDL) calcification aortic valve stenosis VICs/myofibroblasts p38 MAPK IL-6 |
| url | https://www.mdpi.com/2218-273X/13/7/1091 |
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