Abstract-Cardiac extracellular matrix undergoes extensive and continuous turnover involved in the lesion-reparation process, such as in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardial infarction in the transition to heart failure, and during the progression of left ventricular dysfunction. Cardiac fibrosis is a major determinant of diastolic dysfunction and pumping capacity, and it may provide the structural substrate for arrhythmogenicity, thus potentially contributing the to progression of heart failure and sudden death. Aldosterone was shown to promote cardiac fibrosis in various experimental models. It was demonstrated that spironolactone may oppose the effect of aldosterone in promoting cardiac fibrosis. Measurement of cardiac collagen turnover by use of serological markers is a useful tool for monitoring cardiac tissue repair and fibrosis in experimental models or clinical conditions. We found that high serum levels of a marker of collagen turnover (procollagen type III N-terminal peptide ) in patients with chronic heart failure receiving conventional therapy, including ACE inhibitors, was associated with high mortality and hospitalization rates. In RALES (Randomized Aldactone Evaluation Study), in patients randomized to placebo, markers continued to increase or remained unchanged after 6-month follow-up. On the contrary, adding spironolactone 25 mg daily significantly decreased the levels of these serum markers during the same period. Most importantly, the spironolactone-related morbidity and mortality benefit was most predominant in subgroups with highest baseline levels of serum markers. These results suggest that limitation of the aldosterone-related excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with chronic heart failure. Key Words: aldosterone Ⅲ renin-angiotensin system Ⅲ collagen Ⅲ extracellular matrix Ⅲ heart failure I n the myocardium, the role of collagen fibers was thought to be limited to providing a supporting framework for myocytes and blood vessels and acting as lateral connections between muscle bundles. Far from being an inert collection of macromolecules that serves as a scaffold for cells, cardiac extracellular matrix (ECM) undergoes extensive and continuous turnover involved in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, and after myocardial infarction, as well as in the transition to heart failure and during the progression of left ventricular dysfunction. ECM controls numerous cellular functions and serves as a substrate for cell adhesion, a source of anti-apoptotic signals, a reservoir for growth factors, and a determinant of tissue mechanics.Collagen biosynthesis is regulated at different levels of transcription and translation. Type I and type III are the 2 major types of collagen present in the myocardium in both normal and diseased myocardial tissue. Fibrillar collagens within the...