Circulating biomarkers of collagen metabolism in cardiac diseases.

Alterations of the structure and composition of cardiomyocyte and noncardiomyocyte compartments of the myocardium appear to play a central role in the pathogenesis of heart failure (HF) associated with a number of cardiac diseases. Among these alterations, changes in the quantity and quality of the extracellular matrix, including the collagen network, have been characterized that induce remodeling of the myocardium and ultimately deteriorate left ventricular (LV) function and facilitate the development of HF. Studies on circulating biomarkers of collagen metabolism have attracted the attention of the medical community, and some circulating biomarkers have been proposed as potential useful tools to improve diagnosis, prognosis, and therapy in cardiac diseases that develop HF.1 However, the available data are far from conclusive and from affording incremental value to the knowledge provided by more classic diagnostic tools. This is due mainly to 3 limitations. First, collagen is the most abundant protein in the body, and its turnover is so dynamic that not all circulating molecules proposed as biomarkers actually reflect changes in collagen metabolism, namely at the cardiac level. Second, a thorough understanding of the association of a given biomarker with the pathological features of the collagen network in the cardiac disease under study has not been considered essential, thus weakening its pathophysiological meaning. Third, several methodological issues may introduce a number of confounding factors into the measurements of circulating biomarkers of collagen metabolism, thus bringing into question the validity of the available results. Therefore, this article is not aimed at providing a systematic review of all the published information on circulating biomarkers of collagen metabolism in cardiac diseases but at analyzing the biochemical, pathophysiological, and methodological aspects to be taken into account to overcome the above limitations and to improve the clinical applicability of such molecules.