Matrix metalloproteinase and heart failure: is it time to move from research to clinical laboratories?

Abstract

In basic science research laboratories dedicated to heart failure, several substances have been studied as candidate markers of the disease's severity, as target of therapy and as indicators of therapheutical success. Many potential biological markers have emerged and are now under research, among which, markers of myocyte injury (e.g. troponins), markers of inflammation (e.g. tumour necrosis factor α, IL-6), markers of oxidative stress (e.g. urinary byopyrrins), markers of sodium pump activity (e.g. caridiotonics steroids), and a separate group of peptides associated with heart failure.1 However, at present, only natriuretic peptides, in particular, B-type natriuretic peptide, has an established clinical impact. Several reasons account for the frequent failure for substances under research to reach clinical laboratories including the multifactorial causes of heart failure and its progression, the capability/willingness of the manufacturing companies to push, costs and cultural background. Matrix metalloproteinases (MMPs) have a strategic role in the regulation of extracellular collagen matrix turnover, a slow process (t1/2 around 25 days) which, in the heart, is crucial for keeping the most efficient shape of the ventricles. Cardiac repair after a myocardial infarction is a highly complex process that involves temporarily overlapping phases which comprehend inflammation, new tissue formation, and tissue remodelling.2 MMPs are present in the myocardium, are capable of degrading all the matrix components of the heart, and are the driving force behind myocardial matrix remodelling which is responsible for the progressive … *Corresponding author. Tel: +39 02 58002299; fax: +39 02 58002383. E-mail address : piergiuseppe.agostoni{at}ccfm.it