Professor Sian Harding
Stress cardiomyopathy and the b2-adrenoceptor
Professor Harding’s laboratory has a long interest in β2AR signalling in the failing heart. We have begun to study the increasingly recognised syndrome of Stress (Takotsubo) Cardiomyopathy where high adrenaline levels secondary to physical or emotional stress produce acute heart failure with a characteristic apical stunning. The rapid recovery of patients with this syndrome leads us to hypothesise a protective component to the underlying mechanisms (Lyon et al. Nat . Clin. Pract. Cardiovasc. Med. 5, 22-29, 2008). Of particular interest is the predominant demographic of older females, and the relation of this syndrome to other acute heart failure syndromes. Studies in the laboratory have developed a rodent model of Stress Cardiomyopathy and have started to unravel the molecular basis for the effect. These centre on the ability of adrenaline to switch the b2AR to a cardiodepressant but protective Gi coupling. Research opportunities range from molecular biological studies targeting the b2AR and Gi signalling pathways, influences of oestrogens and testosterone, electrophysiological and proarrhythmic consequences, cell survival paradigms, and both screening and development of novel therapeutic strategies for SCM. Many findings offer applicable insights more generally in acute heart failure syndromes. Collaboration with clinical colleagues offers integrated involvement in a proposed national clinical SCM registry, and also stress-induced sudden cardiac death registries. Screening for known b2AR polymorphisms in the clinical population, and functional evaluation of polymorphisms uncovered upon the SCM phenotype, is one example of a potential translational clinical project.
The clinical specialty relevant to: Heart disease, acute coronary syndromes and heart failure.
Further Information
http://www1.imperial.ac.uk/medicine/people/sian.harding/
http://www1.imperial.ac.uk/medicine/about/divisions/nhli/cardio/heart/molcell/fm/
Contact Details
sian.harding@imperial.ac.uk
Tel: +44 (0)20 7351 8146
