Specific alterations in the distribution of extracellular matrix components within rat myocardium during the development of pressure overload.

Cardiac hypertrophy secondary to a sudden aortic pressure overload results in the remodeling of myocytes and extracellular matrix components. Hydroxyproline quantitation to evaluate total collagen content and immunocytochemistry procedures were used to analyze the temporal appearance and regional distribution of collagen, laminin, and fibronectin during the early stages of pressure overload. The study was performed in 25-day-old rats submitted to a thoracic aortic stenosis and killed from 1 day to 18 days after surgery. Cardiac hypertrophy reached 24.5% by day 2 and 75.5% by day 15. Each extracellular matrix component showed a unique distribution throughout the myocardium: in normal hearts, type I/III collagens appeared mainly as large strands or waves around groups of myocytes, fibronectin predominated around small and large vessels, while laminin surrounded both myocytes and capillaries. As early as 2 days after surgery, fibronectin and type I/III collagens, but not laminin, accumulated in focal areas. Thereafter, these areas increased in size and number within the inner part of the left ventricle, and progressively affected the whole left ventricle. Fibronectin accumulation preceded that of collagen and occupied larger areas. The measure of hydroxyproline content demonstrated that during the 1st week after surgery the increase in collagen content is correlated with the increase in heart weight. In conclusion, the three components of the extracellular matrix studied here develop a specific pattern of accumulation in response to a sudden pressure overload that induces cardiac hypertrophy. Both fibronectin and collagen changes participate in the healing of focal myocardial necrosis secondary to the increased hemodynamic work and fibronectin appeared as a more sensitive marker of the cardiac lesions than collagen.