Endothelial Cell Cytoprotection
Professor Justin Mason, Head of Group
As a consequence of its anatomic location at the blood/tissue interface, the vascular endothelium is continuously exposed to potentially harmful factors such as endotoxin, cytokines, complement components, activated leukocytes and oxidatively modified low-density lipoproteins. These contribute to chronic endothelial dysfunction and premature atherosclerosis. Professor Mason leads a basic science research group investigating molecular mechanisms involved in the regulation of vascular endothelial protection. A more detailed understanding of these mechanisms will facilitate the rational design of novel therapies by which the endothelium can be conditioned to minimise vascular injury, endothelial dysfunction and subsequent atherogenesis in patients with systemic inflammatory disease. In addition, he is actively involved in clinical research, which aims to optimise assessment and treatment of the large vessel vasculitides and understand the relationship between chronic endothelial dysfunction and accelerated atherosclerosis.
Current Projects
- The role of protein kinase C isoenzymes in endothelial cytoprotection.
- Investigation of the influence of laminar shear stress on the expression of cytoprotective genes in vascular endothelium.
- Role of heme oxygenase-1 and its products in vascular cytoprotection and angiogenesis.
- Signalling pathways involved in the regulation of endothelial cell anti-apoptotic genes.
- Mechanisms underlying vascular endothelial protection against complement-mediated injury.
The group is currently funded by the British Heart Foundation, Arthritis Research UK and the Wellcome Trust.
Selected Publications
Mason JC. Takayasu’s arteritis - advances in diagnosis and management. Nature Rev Rheumatol 2010; 6: 406-15.
Hamdulay SS, Wang B, Birdsey GM, Ali F, Dumont O, Evans PC, Haskard DO, Wheeler-Jones CP, Mason JC. Celecoxib activates PI-3K/Akt and mitochondrial redox signaling to enhance heme oxygenase-1-mediated anti-inflammatory activity in vascular endothelium. Free Radic Biol Med. 2010 85:701-710.
Ali F; Ali NS; Bauer A; Boyle JJ; Hamdulay SS; Haskard DO; Randi AM; Mason JC. (1 Mar 2010). PPARδ and PGC1α act cooperatively to induce haem oxygenase-1 and enhance vascular endothelial cell resistance to stress. Cardiovasc Res. 85:701-710.
Kinderlerer AR; Gregoire IP; Hamdulay SS; Ali F; Steinberg R; Silva G; Ali N; Wang BF; et al. (12 Feb 2009). Heme oxygenase-1 expression enhances vascular endothelial resistance to complement-mediated injury through induction of decay-accelerating factor: a role for increased bilirubin and ferritin. BLOOD. 113:1598-1607.
Ali F; Zakkar M; Karu K; Lidington EA; Hamdulay SS; Boyle JJ; Zloh M; Bauer A; et al. (10 Jul 2009). Induction of the cytoprotective enzyme heme oxygenase-1 by statins is enhanced in vascular endothelium exposed to laminar shear stress and impaired by disturbed flow. J Biol Chem. 284:18882-18892.
Professor Justin Mason and members of his research group, October 2010
