Cathepsin L was involved in vascular aging by mediating phenotypic transformation of vascular cells.
Arch Gerontol Geriatr
; 104: 104828, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36206719
ABSTRACT
Vascular media and adventitia-induced remodeling plays an important role in vascular aging. However, the mechanism remains unclear. This study aims to investigate the mechanisms underlying vascular aging. Transcriptome analysis revealed that the expression of cathepsin L (CTSL) significantly decreased in arteries of old mice (24 months old) compared with that in arteries of young mice (4 months old), which was confirmed by immunohistochemistry and Western blot. The expression of CTSL in adventitia fibroblasts (AFs) and vascular smooth muscle cells (VSMCs) of aged mice was lower than that of young mice. Compared with wild-type control mice, CTSL knockout (CTSL - /-) mice had increased collagen deposition (fibrosis) and decreased telomerase activity and LC3â
¡/ LC3â
ratio. The expression of mammalian target of rapamycin (mTOR) and osteopontin (OPN) increased in aortas of CTSL-/-mice compared with that in aortas of wild-type control mice. In vitro, lentivirus-mediated CTSL knockdown induced VSMCs senescence and AFs transformed into myofibroblasts (MFs). Rapamycin, a mTOR inhibitor, inhibited CTSL deficiency induced VSMCs senescence, osteopontin (OPN) secretion and AFs migration. In conclusion, the decreased level of CTSL with age may participate in vascular aging by promoting the phenotypic transformation of vascular cells.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Osteopontina
/
Serina-Treonina Quinasas TOR
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Arch Gerontol Geriatr
Año:
2023
Tipo del documento:
Article
País de afiliación:
China