Examining potential therapies targeting myocardial fibrosis through the inhibition of transforming growth factor-beta 1.
After injury, the heart undergoes a remodeling process consisting primarily of myocyte hypertrophy, apoptosis and interstitial fibrosis. Although initially beneficial, excess fibrosis gradually results in alteration of left ventricular properties and cardiac dysfunction. Transforming growth factor-beta 1 (TGF-beta(1)) is thought to be a primary mediator of fibrosis within the heart after injury. Currently, angiotensin II blockade is used to inhibit the actions of TGF-beta(1). However, recent studies indicate that angiotensin II blockade alone may not be sufficient to prevent TGF-beta(1)-induced fibrosis. Thus far, both in vivo and in vitro models have shown that direct TGF-beta(1) inhibition, NAPDH oxidase inhibitors, growth factors and hormonal treatment regimens targeting TGF-beta(1) may significantly reduce cardiac fibrosis after injury. This study attempts to underline these alternatives to angiotensin II blockade in combating TGF-beta(1)-induced cardiac dysfunction.
Khan
Razi
R
McGill University, Faculty of Medicine, Montreal, Canada. razi.khan@gmail.com
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000188:drug therapy*; D016232:Endothelins / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005355:Fibrosis; D013006:Growth Hormone; D017228:Hepatocyte Growth Factor; D006801:Humans; D009206:Myocardium / Q000473:pathology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D045265:Natriuretic Peptides; D009569:Nitric Oxide; D012065:Relaxin; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D004791:Enzyme Inhibitors; D045265:Natriuretic Peptides; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; D012065:Relaxin; D013006:Growth Hormone; D019255:NADPH Oxidases