Emerging therapeutic targets in chronic heart failure: part II.
Chronic heart failure is characterised by functional deficiencies of the myocardium. Structural abnormalities of the left ventricular wall occur in many cases as a consequence of myocardial infarction (MI). The overburdened postMI heart is characterised by an active reorganisation of the remaining myocardium. Increased expression and activity of matrix metalloproteinases lead to altered composition and arrangement of the extracellular matrix, which is accompanied by eccentric hypertrophy of cardiomyocytes. The altered geometry of the heart muscle fosters biomechanical stress, driving the heart into a dead-end situation. Clearly, novel therapeutic concepts must be developed to reverse this process. Part II of the current review will focus on emerging therapeutic targets for small molecule therapeutics in the fields of cardiac remodelling and impaired survival of cardiomyocytes in the diseased heart. Finally, innovative therapeutic concepts for heart gene therapy and replacement options for destroyed post-MI myocardium using embryonic and adult stem cells are described.
Roenicke
Volker
V
Department of Research, MediGene AG, 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
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000502:physiology; D015195:Drug Design; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000502:physiology; D009203:Myocardial Infarction / Q000150:complications; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; D002317:Cardiovascular Agents; D016207:Cytokines; D009124:Muscle Proteins