Fibrosis as a therapeutic target post-myocardial infarction.
The extracellular matrix (ECM) is a dynamic microenvironment and a major contributor to the adverse ventricular remodelling that follows myocardial infarction (MI), via activation of both direct pro-fibrotic pathways and matrix metalloproteinases (MMPs) that enhance collagenase activity. Reactive fibrosis, i.e. deposition of ECM materials remote from the region of the MI is clearly detrimental to ventricular function and contributory to adverse outcomes post-MI. Therefore, reversal of this process represents an important therapeutic target in post-MI management and treatment of established heart failure. A number of existing agents exert their beneficial effects in part via reductions in ECM deposition. Furthermore, specific anti-fibrotic drugs have been developed and are currently being explored for these and other cardiac conditions where pathological ECM deposition is felt to be contributory to disease progression.
See
Fiona
F
National Health & Medical Research Council of Australia Centre of Clinical Research Excellence in Therapeutics, Monash University, Alfred Hospital, Melbourne Victoria 3004, Australia.
Kompa
Andrew
A
Martin
Jennifer
J
Lewis
Dion A
DA
Krum
Henry
H
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D020782:Matrix Metalloproteinases