Mitochondrial DNA and modulation of endothelial cell function by cardiovascular risk factors
Supervisor: Dr Karl Herbert
Endothelial dysfunction characterises many cardiovascular pathologies and is associated with reduced nitric oxide synthesis. We suggest this process may be promoted by the alterations in mitochondrial DNA (mtDNA) that are commonly observed in ageing tissues: mtDNA damage, mutation or deletion. Our recent findings have provided support for the hypothesis that such changes in mtDNA lead to deleterious effects on human endothelial cell phenotype.
The current studentship will investigate whether the effects are reversible by mtDNA reconstitution, the mechanisms whereby mitochondrial factors control nitric oxide bioavailability and the extent to which cardiovascular risk factors also promote changes to mtDNA biochemistry. This studentship will provide generic research training in laboratory and translational medical research, experience in human cell culture and a range of molecular and cellular techniques.
- Enquiries should be directed to: Dr Karl Herbert Tel: 0116 258 3028
Herbert KE, Mistry Y, Hastings R, Poolman T, Niklason L, Williams B (2008). Angiotensin II-mediated oxidative DNA damage accelerates cellular senescence in cultured human vascular smooth muscle cells via telomere-dependent and independent pathways. Circ. Res. 102: 201-8.
Wilson WR, Herbert KE, Mistry Y, Stevens SE, Patel HR, Hastings RA, Thompson MM, Williams B (2008) Blood leucocyte telomere DNA content predicts vascular telomere DNA content in humans with and without vascular disease. Eur Heart J 29: 2689-94.