title: In search of new therapeutic targets and strategies for heart failure: recent advances in basic science.
abstract: Chronic heart failure continues to impose a substantial health-care burden, despite recent treatment advances. The key pathophysiological process that ultimately leads to chronic heart failure is cardiac remodelling in response to chronic disease stresses. Here, we review recent advances in our understanding of molecular and cellular mechanisms that play a part in the complex remodelling process, with a focus on key molecules and pathways that might be suitable targets for therapeutic manipulation. Such pathways include those that regulate cardiac myocyte hypertrophy, calcium homoeostasis, energetics, and cell survival, and processes that take place outside the cardiac myocyte--eg, in the myocardial vasculature and extracellular matrix. We also discuss major gaps in our current understanding, take a critical look at conventional approaches to target discovery that have been used to date, and consider new investigational avenues that might accelerate clinically relevant discovery.
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, London, UK. ajay.shah@kcl.ac.uk
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D003326:Coronary Circulation; D005109:Extracellular Matrix / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D002118:Calcium