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.

Základní údaje

Originální název

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

Autoři

BELAKOVA, Barbora (40 Rakousko), Nicholas K WEDIGE (40 Rakousko), Ezzat M AWAD (40 Rakousko), Simon HESS (40 Rakousko), Andre OSZWALD (40 Rakousko), Marlene FELLNER (40 Rakousko), Shafaat Y KHAN (40 Rakousko), Ulrike RESCH (40 Rakousko), Markus LIPOVAC (40 Rakousko), Karel ŠMEJKAL (203 Česká republika, domácí), Pavel UHRIN (40 Rakousko), Johannes M BREUSS (40 Rakousko), Kay-Dietrich WAGNER (250 Francie) a Ping SONG (156 Čína)

Vydání

Cells, BASEL, 2023, 2073-4409

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.000 v roce 2022

Kód RIV

RIV/00216224:14160/23:00133784

Organizační jednotka

Farmaceutická fakulta

DOI

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

UT WoS

001131066200001

Klíčová slova anglicky

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

Štítky

rivok, ÚPL

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 16. 3. 2024 17:46, RNDr. Pavel Šmerk, Ph.D.

Anotace

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.

Návaznosti

GF21-38204L, projekt VaV

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

Investor: Grantová agentura ČR, Komplexy vybraných přechodných kovů s rostlinnými látkami s anti-NF-kappa B a pro-PPAR duální aktivitou, Partnerská agentura (Rakousko)

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 a Ping SONG. Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death. Cells. BASEL, 2023, roč. 12, č. 24, s. 2836-2856. ISSN 2073-4409. Dostupné z: 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 a Ping SONG. Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death. \textit{Cells}. BASEL, 2023, roč.~12, č.~24, s.~2836-2856. ISSN~2073-4409. Dostupné z: https://dx.doi.org/10.3390/cells12242836.

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