Collagen is the major
extracellular matrix protein in the heart and represents a crucial target for anti-remodeling and cardioprotective
therapy.
Collagen quantity and quality have been shown to be regulated under various physiological and pathologic conditions. Excessive deposition of
collagen, leading to cardiac
fibrosis, is a major determinant of cardiac dysfunction and arrhythmogenecity associated with
sudden death. Serological markers of
collagen turnover were proven as a noninvasive reliable tool for monitoring from a distance cardiac tissue repair and
fibrosis, both in experimental and clinical conditions. Some markers of
collagen synthesis and degradation were shown to have a prognostic significance in
myocardial infarction,
cardiomyopathy and
heart failure, and were reported as independent predictors of mortality.
Aldosterone represents the end-product of the renin angiotensin aldosterone system and may play a role in cardiac
collagen deposition independent of its effect on blood pressure. Production of
aldosterone is mainly regulated by
angiotensin II and is activated in the failing human ventricle in proportion to
heart failure severity. Circulating or locally produced
aldosterone stimulates
fibrillar collagen accumulation in the heart directly via
mineralocorticoid receptors or, indirectly, modifying angiotensine II receptors number and/or function. The use of
mineralocorticoid receptor antagonists counters
collagen deposition, even when used on top of classical RAAS inhibitors, such as
ACE inhibitors and angiotensine II receptor blockers. There is now accumulating evidence from experimental and clinical studies showing antifibrotic and cardioprotective effect for
aldosterone antagonists,
spironolactone and
eplerenone. In chronic
heart failure and post
myocardial infarction patients,
aldosterone receptor blockade benefit was associated with decreased serum levels of
collagen synthesis marker
PIIINP (
procollagen type III amino-terminal
peptide), without affecting
collagen degradation. Understanding various autocrine/paracrine mechanisms involved in extracellular matrix remodeling in
heart failure represents a major challenge, essential for developing new cardioreparative and cardioprotective strategies.