Increase in cross-linking of type I and type III collagens associated with volume-overload hypertrophy

Types I, III, IV, and V collagen were isolated and characterized from eight normal dog hearts and seven with volume-overload hypertrophy. Animals with volume-overload hypertrophy were killed at a time when left ventricular end-diastolic pressure and stiffness were increased. The collagens were characterized by solubility properties, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and enzyme-linked immunosorbent assay. The percentage of collagen obtained from canine left ventricles was decreased from 32.4% in normal hearts to 15.0% in hypertrophied hearts. We attribute this to a diminution in the extractability of types I and III collagen, which fell from 199.5 mg type I/g collagen and 76.4 mg type III/g collagen in normal hearts to 83.5 mg type I/g collagen and 26.4 mg type III/g collagen in hypertrophied hearts. The amount of types IV and V collagen isolated remained constant in both the control and arteriovenous shunt hearts averaging 15.7 mg type IV/g collagen and 32.1 mg type V/g collagen in control hearts and 12.5 mg type IV/g collagen and 28.9 mg type V/g collagen in hypertrophied hearts. The reduction in quantity of types I and III collagen probably reflects a greater degree of cross-linking in these two types of collagen. Cyanogen bromide peptide analysis confirmed that there was an increase of high molecular weight cross-linked peptides from 3.96% in normal samples to 8.88% in hypertrophied samples. We conclude that cross-linking of types I and III collagen increases in volume-overload hypertrophy and that this is associated with a rise in diastolic stiffness.