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Cells 2016, 5(4), 41;

Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells

British Heart Foundation Centre of Research Excellence, Cardiovascular Division, King’s College London, London SE5 9NU, UK
Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London SE1 1UL, UK
MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
Author to whom correspondence should be addressed.
Academic Editor: Thomas Dechat
Received: 15 September 2016 / Revised: 10 November 2016 / Accepted: 11 November 2016 / Published: 15 November 2016
(This article belongs to the Collection Lamins and Laminopathies)
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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. View Full-Text
Keywords: prelamin A; migratory persistence; Rac1 prelamin A; migratory persistence; Rac1

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Porter, L.J.; Holt, M.R.; Soong, D.; Shanahan, C.M.; Warren, D.T. Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells. Cells 2016, 5, 41.

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