Dokument: Smoke Condensate-Induced Vascular Senescence and SASP Are Attenuated by Dual mTORC1/2 Inhibition with Rapalink-1

Titel:	Smoke Condensate-Induced Vascular Senescence and SASP Are Attenuated by Dual mTORC1/2 Inhibition with Rapalink-1
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=73633
URN (NBN):	urn:nbn:de:hbz:061-20260616-125052-0
Kollektion:	Publikationen
Sprache:	Englisch
Dokumententyp:	Wissenschaftliche Texte » Artikel, Aufsatz
Medientyp:	Text
Autoren:	You, Jinliang [Autor] Liu, Hongjun [Autor] Khan, Dilaware [Autor] Muhereza, Robert [Autor] Faust, Katharina [Autor] Muhammad, Sajjad [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 6,36 MB in einer Datei [ZIP-Datei erzeugen] Dateien vom 16.06.2026 / geändert 16.06.2026
Stichwörter:	vascular senescence , SASP , mTOR , rapalink-1
Beschreibung:	Cigarette smoking contributes to vascular aging through oxidative stress, inflammation, and extracellular matrix (ECM) remodeling. Cellular senescence has been recognized as an important mechanism linking tobacco exposure to vascular dysfunction, but effective pharmacological strategies targeting this process remain scarce. In this study, we examined whether Rapalink-1, a dual inhibitor of mechanistic target of rapamycin complex 1 and complex 2 (mTORC1 and mTORC2), modulates smoke condensate (SC)-induced senescence in vascular cells. Human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs) were exposed to SC with or without Rapalink-1. SC increased intracellular reactive oxygen species, induced DNA damage, and promoted senescence-associated changes, including increased senescence-associated β-galactosidase (SA-β-gal) activity, reduced Lamin B1, and elevated p21 expression. These effects were accompanied by increased expression of inflammatory and matrix-remodeling genes associated with the senescence-associated secretory phenotype (SASP). Rapalink-1 co-treatment reduced oxidative stress and DNA damage, attenuated senescence markers, and partially normalized SASP-related and ECM-associated gene expression. Mechanistically, SC activated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling and increased downstream mTOR pathway activity, whereas Rapalink-1 dampened these signaling responses. Together, these findings indicate that dual mTORC1/2 inhibition by Rapalink-1 mitigates smoke condensate-induced senescence and inflammatory responses in vascular cells.
Rechtliche Vermerke:	Originalveröffentlichung: You, J., Liu, H., Khan, D., Muhereza, R., Faust, K., & Muhammad, S. (2026). Smoke Condensate-Induced Vascular Senescence and SASP Are Attenuated by Dual mTORC1/2 Inhibition with Rapalink-1. International Journal of Molecular Sciences, 27(8), Article 3636. https://doi.org/10.3390/ijms27083636
Lizenz:	Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Fachbereich / Einrichtung:	Medizinische Fakultät
Dokument erstellt am:	16.06.2026
Dateien geändert am:	16.06.2026