You are here: Home BHF Centre of Research Excellence Researchers Barbara Casadei

Barbara Casadei MD, DPhil, FRCP, FESC

Professor of Cardiovascular Medicine, Honorary Consultant Cardiologist and Senior Research Fellow
Heart failure and calcium signalling, genetic determinants of cardiac pacemaker activity

Divisional Research Themes

  • Cardiovascular Science

Cardiovascular subthemes

Group Members

  • Yin Hua Zhang, MD, PhD, Senior postdoctoral scientist
  • Dr Ricardo Carnicer, PhD, Postdoctoral scientist
  • Mei Hua Zhang, PhD, Senior postdoctoral scientist
  • Winifred O Idigo, DPhil student
  • Svetlana Reilly, DPhil student
  • Gregory Lim, DPhil student


Web Personal Website
Tel 01865 234664
Fax 01865 234667
PA Ms Eunice Berry
Email (PA)
Contact address Division of Cardiovascular Medicine, Level 6, West Wing, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom
Department Division of Cardiovascular Medicine
Radcliffe Department of Medicine
College Green Templeton College
Barbara Casadei

Prof Barbara Casadei

The focus of our research programme is to understand the role of nitric oxide (NO) and reactive oxygen species (ROS) in the regulation of cardiac function in health and disease. Our early work showed that NO can directly increase heart rate by stimulating the hyperpolarisation-activated 'pace-maker' current, If, in sinoatrial node cells via a sGC/cGMP dependent signalling pathway (Musialek et al.1997). We tested the functional relevance of this finding in vivo and showed that the NO- If pathway contributes to the positive chronotropic effect of nitrovasodilators in humans (Hogan et al.1999a, Hogan et al.1999b) and may be involved in the tonic regulation of heart rate by endogenously produced NO (Musialek et al.1999). Moreover, we demonstrated that stimulation of cAMP signalling (through cGMP-induced inhibition of PDE3) plays an important role in the NO/cGMP-mediated stimulation of If in the sinoatrial node (Musialek et al.2000) but not in the hypertrophied left ventricular myocardium, where NO and cGMP signalling appear to be uncoupled (Bryant et al.2001).

Our current interest in the pathogenesis of cardiac failure and atrial fibrillation stems from the identification in 2002 of a novel mechanism by which a ‘neuronal’ isoform of NO synthase (nNOS) localised to the mammalian myocardium modulates cardiac function in vivo and at the single cell level by regulating key myocardial Ca2+ fluxes (i.e., the L-type Ca2+ current and the activity the sarcoplasmic Ca2+ pump or SERCA2a) (Ashley et al., 2002, Sears et al. 2003, Martin et al. 2006, Zhang et al. 2007). As the initiation and progression of heart failure involves defective Ca2+ regulation, nNOS-derived NO may play an important role in the myocardial response to stress. Indeed, we and others have shown that nNOS expression and activity are significantly increased in the failing myocardium and that nNOS gene disruption is associated with a more pronounced left ventricular dilatation and with a severely depressed beta-adrenergic reserve 8 weeks after myocardial infarction (Dawson, Lygate et al. 2005). These data suggest that nNOS upregulation in the infarcted myocardium may be a protective mechanism aimed at maintaining myocardial Ca2+ homeostasis. We now want to take this work forward by elucidating the subcellular and molecular mechanisms that underlie the myocardial effects of nNOS and by better understanding the role of nNOS-derived NO in the human myocardium.

A recurrent motif in cardiovascular pathophysiology is that compensatory mechanisms that are effective in counterbalancing the adverse effects of myocardial injury become pathogenic when sustained over the long term. For instance, in disease states NOS activity may be altered by the reduced availability of essential co-factors; under these conditions NOS upregulation can become pathogenic, as the synthase becomes enzymatically ‘uncoupled’ and synthesises ROS rather than NO.

Our work has provided the first evidence that this putative mechanism is relevant to the human myocardium (Kim et al.2005). We found that the main source of superoxide production and the likely cause of NOS uncoupling in atrial myocytes from patients with atrial fibrillation is a phagocytic-type NAD(P)H oxidase (Kim et al. 2005). Furthermore, in a study that recruited 170 consecutive patients undergoing cardiac surgery we have recently demonstrated that myocardial NAD(P)H oxidase activity is an independent predictor of atrial fibrillation in the post-operative period (Kim et al. 2007). We are now investigating whether myocardial ROS formation is involved in the electrical and structural remodelling that is induced by atrial fibrillation.

We use an integrative approach linking basic science to clinical investigations. This has proved to be an efficient way of testing hypotheses and has provided a stimulating training environment for both medical and science graduates.

Several trainees in our group have been awarded prestigious prizes/fellowships (e.g., Dr Claire Sears, Dorothy Hodgkin Fellow of the Royal Society, was awarded the Melvin L. Marcus Young Investigator Award of the American Heart Association in 2002).

We are keen to recruit talented and enthusiastic researchers with an interest in heart failure or atrial fibrillation.

Sources of Funding