BHF Cardiovascular Research Group

Human essential hypertension is a complex, multifactorial, quantitative trait under a polygenic control. Over the last decade several strategies have been used to dissect the genetic determinants of hypertension. Attempts to identify the multiple genes involved in the more common polygenic form of hypertension has been more difficult.

The study of human essential hypertension can be carried out using two basic molecular genetic approaches, association and linkage analysis. Recent data published by our own group have implicated genes involved in oxidant homeostasis on blood pressure regulation.

The use of microarrays on an experimental model of hypertension have shown that the gene, glutathione S transferase, involved in defence of oxidant stress, is differentially expressed in the kidney. It has become more evident that the study of single genes in a complex disorder such as essential hypertension may not be sufficient in dissecting the genetic etiology of this disease. The use of new molecular tools such as gene “chips” or microarrays for either gene expression profiling or single nucleotide polymorphisms (SNPs) based total genome scanning strategies will ultimately result in new diagnostics and therapeutics for human essential hypertension

Gene transfer/ therapy is a promising approach for both furthering our understanding of the molecular basis of (patho)physiological pathways and the development of molecular therapies for the treatment of cardiovascular disease. Previous work from our group have demonstrated proof of concept for the ability of viral vectors to mediate therapeutic transgene expression locally in diverse models of cardiovascular disease, including hypertension and vein graft failure. However, it has now clear that current gene delivery vectors require optimisation to improve their safety and efficiency if clinical gene therapy is to become a reality. We are developing viral gene delivery vectors (adenovirus and adeno-associated virus) that are modified such that they can deliver transgene expression selectively and efficiently to defined tissues in vivo after systemic delivery.

The development and refinement of these vectors will enable us to deliver candidate genes to defined tissues in vivo, both for characterising the molecular mechanisms of cardiovascular disease and ultimately for the development of safe and efficient clinical cardiovascular gene therapy.

The BHF Cardiovascular research group aims to carry out research on genetics and vascular biology applied to cardiovascular disease.