Abstract
Vascular smooth muscle cell (VSMC) motility is essential during both physiological and pathological vessel remodeling. Although ageing has emerged as a major risk factor in the development of cardiovascular disease, our understanding of the impact of ageing on VSMC motility remains limited. Prelamin A accumulation is known to drive VSMC ageing and we show that presenescent VSMCs, that have accumulated prelamin A, display increased focal adhesion dynamics, augmented migrational velocity/persistence and attenuated Rac1 activity. Importantly, prelamin A accumulation in proliferative VSMCs, induced by depletion of the prelamin A processing enzyme FACE1, recapitulated the focal adhesion, migrational persistence and Rac1 phenotypes observed in presenescent VSMCs. Moreover, lamin A/C-depleted VSMCs also display reduced Rac1 activity, suggesting that prelamin A influences Rac1 activity by interfering with lamin A/C function at the nuclear envelope. Taken together, these data demonstrate that lamin A/C maintains Rac1 activity in VSMCs and prelamin A disrupts lamin A/C function to reduce Rac1 activity and induce migrational persistence during VSMC ageing.
Original language | English |
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Article number | 41 |
Journal | Cells |
Volume | 5 |
Issue number | 4 |
Early online date | 15 Nov 2016 |
DOIs | |
Publication status | Published - Dec 2016 |
Keywords
- prelamin A
- migratory persistence
- Rac1
Profiles
-
Derek Warren
- School of Chemistry, Pharmacy and Pharmacology - Associate Professor in Pharmacology
- Molecular and Tissue Pharmacology - Member
Person: Research Group Member, Academic, Teaching & Research