Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death
Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds tha...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/24/2836 |
| _version_ | 1797381662726684672 |
|---|---|
| author | Barbora Belakova Nicholas K. Wedige Ezzat M. Awad Simon Hess André Oszwald Marlene Fellner Shafaat Y. Khan Ulrike Resch Markus Lipovac Karel Šmejkal Pavel Uhrin Johannes M. Breuss |
| author_facet | Barbora Belakova Nicholas K. Wedige Ezzat M. Awad Simon Hess André Oszwald Marlene Fellner Shafaat Y. Khan Ulrike Resch Markus Lipovac Karel Šmejkal Pavel Uhrin Johannes M. Breuss |
| author_sort | Barbora Belakova |
| collection | DOAJ |
| description | Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy. |
| first_indexed | 2024-03-08T20:54:39Z |
| format | Article |
| id | doaj.art-541bee0379d64455a4b0c42b2271e9bf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T20:54:39Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-541bee0379d64455a4b0c42b2271e9bf2023-12-22T13:59:45ZengMDPI AGCells2073-44092023-12-011224283610.3390/cells12242836Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell DeathBarbora Belakova0Nicholas K. Wedige1Ezzat M. Awad2Simon Hess3André Oszwald4Marlene Fellner5Shafaat Y. Khan6Ulrike Resch7Markus Lipovac8Karel Šmejkal9Pavel Uhrin10Johannes M. Breuss11Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaKarl Landsteiner Institute for Cell-Based Therapy in Gynecology, 2100 Korneuburg, AustriaDepartment of Natural Drugs, Faculty of Pharmacy, Masaryk University, 612 00 Brno, Czech RepublicInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaPre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy.https://www.mdpi.com/2073-4409/12/24/2836endothelial cellssenescencesenolyticsstatinsanoikisapoptosis |
| spellingShingle | Barbora Belakova Nicholas K. Wedige Ezzat M. Awad Simon Hess André Oszwald Marlene Fellner Shafaat Y. Khan Ulrike Resch Markus Lipovac Karel Šmejkal Pavel Uhrin Johannes M. Breuss Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death Cells endothelial cells senescence senolytics statins anoikis apoptosis |
| title | Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death |
| title_full | Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death |
| title_fullStr | Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death |
| title_full_unstemmed | Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death |
| title_short | Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death |
| title_sort | lipophilic statins eliminate senescent endothelial cells by inducing anoikis related cell death |
| topic | endothelial cells senescence senolytics statins anoikis apoptosis |
| url | https://www.mdpi.com/2073-4409/12/24/2836 |
| work_keys_str_mv | AT barborabelakova lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT nicholaskwedige lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT ezzatmawad lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT simonhess lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT andreoszwald lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT marlenefellner lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT shafaatykhan lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT ulrikeresch lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT markuslipovac lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT karelsmejkal lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT paveluhrin lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath AT johannesmbreuss lipophilicstatinseliminatesenescentendothelialcellsbyinducinganoikisrelatedcelldeath |