Martin Bennett (United Kingdom)

University of Cambridge Section of CardioRespiratory Medicine
Professor Bennett trained in Cardiology in Birmingham and Cambridge. He was awarded one of the very first BHF 7-year Clinician Scientist Fellowships in 1990 and undertook research training at the Imperial Cancer Research Fund Laboratories, London, studying vascular smooth muscle cell (VSMC) division and cell death in atherosclerosis and arterial injury. This was followed by a post-doctoral position in Seattle, USA, and later award of a BHF Senior Fellowship in 1997. He currently holds the British Heart Foundation Chair of Cardiovascular Sciences at the University of Cambridge, with Honorary Consultant Cardiologist positions at Addenbrooke's and Papworth Hospitals, and heads the Section of CardioRespiratory Medicine in Cambridge. Professor Bennett directs the BHF Cambridge Centre for Cardiovascular Research Excellence, and BHF Cambridge PhD programme in Cardiovascular Research. His major research interest is the vascular biology of atherosclerosis and artery development, and has identified the mechanisms and consequences of VSMC apoptosis and cell senescence in atherosclerosis. His clinical research programme examines the ability of invasive and non-invasive coronary artery imaging to identify vulnerable plaques, focussing particularly on VH-IVUS and CT. Professor Bennett has published widely on these subjects, and is currently on the editorial board of Circulation Research. In 2007 he was elected to the Academy of Medical Sciences and was the Chairman of the British Atherosclerosis Society until 2014.

Author Of 2 Presentations

Role of SIRT 1 and 6 in mitochondrial dysfunction and cardiovascular diseases (ID 1291)

Session Type
Genetics
Session Time
14:30 - 16:00
Date
Tue, 01.06.2021
Room
Hall D
Lecture Time
14:33 - 14:48

O068 - Telomere damage promotes vascular smooth muscle cell senescence and immune cell recruitment after vessel injury (ID 194)

Session Type
Vascular Biology
Session Time
10:30 - 12:00
Date
Wed, 02.06.2021
Room
Live Streamed
Lecture Time
11:27 - 11:35

Abstract

Background and Aims

Background and Aims: Vascular smooth muscle cells (VSMCs) accumulate in injury-induced neointimal lesions and atherosclerotic plaques in an oligoclonal fashion, yet plaque VSMCs show reduced proliferation and cell senescence. DNA damage leads to VSMC senescence and inflammation and VSMC senescence promotes atherosclerosis; however, the exact mechanism by which VSMC senescence promotes lesion formation is not known. Here, we investigated telomere damage-induced VSMC senescence, the contribution of senescence-induced inflammation and the mechanisms involved, the consequences of VSMC senescence in vivo after injury, and whether it promotes clonality.

Methods

Methods: Stress-induced premature senescence (SIPS) was induced by doxorubicin (24h treatment+21d recovery). Lentiviruses were used to stably overexpress a dysfunctional TRF2 mutant protein (TRF2T188A) in hVSMCs. SM22αTRF2T188A mice were generated that express human TRF2T188A in VSMCs only, and crossed with Myh11-CreERT2 Rosa26-Confetti multicolour reporter mice to examine cell senescence and clonality in vivo.

Results

Results: Both SIPS and TRF2188A-induced VSMC senescence were characterised by persistent telomere damage, and associated with formation of micronuclei, activation of cGAS-STING cytoplasmic DNA sensing, and induction of multiple pro-inflammatory cytokines. Silencing of cGAS in TRF2T188A hVSMCs partially inhibited NFκB-dependent cytokine expression. In vivo, VSMC-specific TRF2T188A expression in a multicolour VSMC-tracking model demonstrated no change in VSMC clonal patches after injury, but increased neointima formation, outward remodelling, and immune/inflammatory cell infiltration or retention.

Conclusions

Conclusion: Persistent telomere damage promotes VSMC senescence and inflammation and exacerbates neointima formation after injury. Our data suggest that persistent telomere damage-induced VSMC senescence plays a major role in driving inflammation through immune cell recruitment in vascular disease.

Hide

Presenter of 1 Presentation

Role of SIRT 1 and 6 in mitochondrial dysfunction and cardiovascular diseases (ID 1291)

Session Type
Genetics
Session Time
14:30 - 16:00
Date
Tue, 01.06.2021
Room
Hall D
Lecture Time
14:33 - 14:48