Emerging therapeutic targets in chronic heart failure: part I.
Chronic heart failure (CHF) is a life threatening disease with an enormous medical requirement. Approximately 15 million people worldwide suffer from CHF. The prevalence will inevitably increase due to the ageing population. Nevertheless, current treatment options based on angiotensin-converting enzyme inhibitors and beta-adrenergic receptor antagonists merely slow progression of the disease. Novel treatment concepts based on new therapeutic targets must have the capability to reverse the severity of this disease. This review, focusing on the emerging targets in the most promising therapeutic areas for the treatment of CHF, will be divided into two parts. In Part I, disease concepts such as altered calcium handling and ion channel activity, pathophysiological hypertrophy and inefficient cardiac metabolism are discussed. Validation status and potential therapeutic value for new targets in each research field is given by summarising the results of in vitro and in vivo studies.
Roenicke
Volker
V
MediGene AG, Lochhamer Str. 11, 82152 Martinsried, Germany.
Leclair
Stéphane
S
Hoffmann
Anke
A
Becker
Michael
M
Szado
Tania
T
Kirsch
Thomas
T
Stoss
Oliver
O
Navé
Barbara T
BT
Henkel
Thomas
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D047493:PPAR alpha / Q000502:physiology; D051381:Rats; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002317:Cardiovascular Agents; D005227:Fatty Acids; D007473:Ion Channels; D009124:Muscle Proteins; D047493:PPAR alpha; D014157:Transcription Factors