Lipophilic Statins Eliminate Senescent Endothelial Cells by
inducing Anoikis-Related Cell Death

J 2023

Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death

BELAKOVA, Barbora, Nicholas K WEDIGE, Ezzat M AWAD, Simon HESS, Andre OSZWALD et. al.

Basic information

Original name

Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death

Authors

BELAKOVA, Barbora (40 Austria), Nicholas K WEDIGE (40 Austria), Ezzat M AWAD (40 Austria), Simon HESS (40 Austria), Andre OSZWALD (40 Austria), Marlene FELLNER (40 Austria), Shafaat Y KHAN (40 Austria), Ulrike RESCH (40 Austria), Markus LIPOVAC (40 Austria), Karel ŠMEJKAL (203 Czech Republic, belonging to the institution), Pavel UHRIN (40 Austria), Johannes M BREUSS (40 Austria), Kay-Dietrich WAGNER (250 France) and Ping SONG (156 China)

Edition

Cells, BASEL, 2023, 2073-4409

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.000 in 2022

RIV identification code

RIV/00216224:14160/23:00133784

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3390/cells12242836

UT WoS

001131066200001

Keywords in English

endothelial cells; senescence; senolytics; statins; anoikis; apoptosis

Abstract

V originále

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.

Links

GF21-38204L, research and development project

Name: Komplexy vybraných přechodných kovů s rostlinnými látkami s anti-NF-kappa B a pro-PPAR duální aktivitou

Investor: Czech Science Foundation, Partner Agency (Austria)

Citovat

BELAKOVA, Barbora, Nicholas K WEDIGE, Ezzat M AWAD, Simon HESS, Andre OSZWALD, Marlene FELLNER, Shafaat Y KHAN, Ulrike RESCH, Markus LIPOVAC, Karel ŠMEJKAL, Pavel UHRIN, Johannes M BREUSS, Kay-Dietrich WAGNER and Ping SONG. Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death. Cells. BASEL, 2023, vol. 12, No 24, p. 2836-2856. ISSN 2073-4409. Available from: https://dx.doi.org/10.3390/cells12242836.

@article{2384404,
   author = {Belakova, Barbora and Wedige, Nicholas K and Awad, Ezzat M and Hess, Simon and Oszwald, Andre and Fellner, Marlene and Khan, Shafaat Y and Resch, Ulrike and Lipovac, Markus and Šmejkal, Karel and Uhrin, Pavel and Breuss, Johannes M and Wagner, KayandDietrich and Song, Ping},
   article_location = {BASEL},
   article_number = {24},
   doi = {http://dx.doi.org/10.3390/cells12242836},
   keywords = {endothelial cells; senescence; senolytics; statins; anoikis; apoptosis},
   language = {eng},
   issn = {2073-4409},
   journal = {Cells},
   title = {Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death},
   url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10742095/},
   volume = {12},
   year = {2023}
}

TY  - JOUR
ID  - 2384404
AU  - Belakova, Barbora - Wedige, Nicholas K - Awad, Ezzat M - Hess, Simon - Oszwald, Andre - Fellner, Marlene - Khan, Shafaat Y - Resch, Ulrike - Lipovac, Markus - Šmejkal, Karel - Uhrin, Pavel - Breuss, Johannes M - Wagner, Kay-Dietrich - Song, Ping
PY  - 2023
TI  - Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death
JF  - Cells
VL  - 12
IS  - 24
SP  - 2836
EP  - 2836
SN  - 20734409
KW  - endothelial cells
KW  - senescence
KW  - senolytics
KW  - statins
KW  - anoikis
KW  - apoptosis
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10742095/
N2  - 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.
ER  -

BELAKOVA, Barbora, Nicholas K WEDIGE, Ezzat M AWAD, Simon HESS, Andre OSZWALD, Marlene FELLNER, Shafaat Y KHAN, Ulrike RESCH, Markus LIPOVAC, Karel ŠMEJKAL, Pavel UHRIN, Johannes M BREUSS, Kay-Dietrich WAGNER and Ping SONG. Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death. \textit{Cells}. BASEL, 2023, vol.~12, No~24, p.~2836-2856. ISSN~2073-4409. Available from: https://dx.doi.org/10.3390/cells12242836.

Detailed Information on Publication Record