Hiten Mistry

Biography

Self Biography  My main research interests are in the pathophysiology of the hypertensive diseases of pregnancy and intrauterine growth restriction. Pre-eclampsia remains a common disorder in pregnancy, affecting 3-5% of all UK pregnancies. Pre-eclampsia is a state of elevated oxidative stress; reduced placental perfusion or ischaemic reperfusion play a critical role in excessive generation of reactive oxygen species (ROS), which are thought to initiate a cascade of events in susceptible individuals leading to maternal oxidative stress and endothelial cell dysfunction.

Research Interest

Salt, aldosterone in pregnancy and pre-eclampsia: This particular BHF funded research has been developed out of valuable European collaborations (Professor Markus Mohaupt (Bern)): the primary aim is to determine the association between aldosterone, salt (via salt sensing), angiogenic and proinflammatory markers in relation to placentation, normal pregnancy and the aetiology of pre-eclampsia. We hope this study will inform future interventions for reducing disease prevalence, possibly by simple dietary adjustments. It may also provide biomarkers in early pregnancy for identification of women at risk of pre-eclampsia and for allocation of proper preventive strategies, which by early instigation may improve placentation. Placental renin-angiotensin system (RAS) in pregnancy: In collaboration with Professors Broughton Pipkin, Dr Lesia Kurlak (Nottingham) and Burton (Cambridge), I am studying the potential role of the RAS in very early placentation, together with assessment of its systemic impact. The redox balance markedly influences the capacity to generate angiotensin I, and hence angiotensin II (AngII), from angiotensinogen: AngII exerts much of its vasoconstrictor effect by the generation of reactive oxygen species. Placentation occurs at very low oxygen tensions, and we have increasing evidence for the involvement of the RAS and associated pathways in trophoblast invasion due to changes under both chronic and acute hypoxic conditions. These investigations have been performed using a small bank of well-characterised placental tissue to which I have access and includes, maternal and fetal plasma and serum samples from pre-eclamptic and age- and BMI-matched controls. These archived samples and an on-going collection of placental tissue could be available for future studies within this post. Below are some of the main reaseach areas our group is working on at present: Placental lipoproteins and caveolae: Abnormal lipid metabolism may be involved in the pathogenesis of pre-eclampsia with lesions in the pre-eclamptic uteroplacental bed resembling those of atherosclerosis. Atherosclerosis is characterised by increased expression of a number of lipoprotein receptors. We are currently working directly with Professors Carlos de Figueiredo & Bartira da Costa (PUCRS, Brazil) to investigate the placental expression of these genes in pre-eclampsia. This is one of the first detailed placental mRNA expression profiles of lipoprotein receptors, coupled with maternal and fetal lipoprotein concentrations from pre-eclamptic and control placentae. We are also investigating the mRNA and protein expression together with localisation of the components of the lipid raft caveolae. Antioxidant micronutrients and enzymes in pregnancy: There is growing evidence, including collaborative research at King's College London (Professor Lucialla Poston and Dr. Kate Bramham) and Nottingham (Dr. Lesia Kurlak, Professor Fiona Broughton Pipkin & Dr. Linda morgan) that inadequate antioxidant defences play a major role in the generation of oxidative stress and this is confounded by sub-optimal micronutrient status. This BHF fundded work aims to provide in-depth mechanistic detail of antioxidant micronutrients and related enzyme activities in the development of pre-eclampsia. Micronutrient concentrations and various antioxidant enzyme activities have been measured in plasma obtained at 15 weeks' gestation from women who subsequently developed pre-eclampsia and from matched women with normal pregnancy outcome. Single nucleotide polymorphisms which influence activity of these antioxidant enzymes have been assessed as possible confounders. All samples have been obtained from an international consortium of eight Universities (SCreening fOr Pregnancy Endpoints; SCOPE) which has successfully recruited 5340 women. Our interest in antioxidant capacity in pregnancy links to the problem of selenium deficiency. We am actively developing collaborations between KCL, the Universities of Nottingham, East Anglia and Blantyre (Malawi), to carry out a study into selenium soil enrichment in Malawi in relation to pregnancy. The emphasis of this research is on the improvement of nutrition and wellbeing in pregnant women in whom obstetric complications are worryingly high. This study would fit in with the 5th Millennium Development Goal. Urinary proteomics for the diagnosis and predictions of pre-eclampsia: This collaborative (Professor Lucialla Poston and Dr. Kate Bramham and Dr. Malcolm Ward, KCL) research investigates the urinary proteome with the aim of identifying potential biomarkers in human pregnancies to improve the diagnosis and/or prediction of pre-eclampsia. To investigate predictive biomarkers, urine specimens collected at 15 weeks' gestation from low-risk women who later develop pre-eclampsia have been compared with those that progressed with a healthy pregnancy and the urinary proteome analysed for newly defined candidate biomarkers.