Biomechanics on Remodeling of Biological Tissues - Role of Collagen Cross-Linking

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The area fractions of collagen and elastin in the rat common carotid artery did not change between 8 and 64 weeks, whereas the elastic modulus of wall was significantly larger in 64 weeks old animals compared to younger ones. To know the reason, we have applied a hydromechanical isometric tension method to the analysis of cross-linking of collagen. In the method, a tissue specimen is stretched and heated to above collagen denaturation temperature, and kept at this temperature under constant strain condition. Stress relaxation observed thereafter indicates a measure of the amount of thermally stable, matured cross-linking ; stress reduction is a measure of cross-linking.First, we studies age-related changes of cross-linking in arterial wall using rat common carotid arteries aged 8, 16, 32, and 64 weeks. Small rectangular specimens were attached to a specially designed test apparatus, and immersed in distilled water in a thermostatic bath. While a tensile strain (in vivo strain) was applied to each specimen, specimen temperature was elevated to 100C. While the specimen was kept under this condition, force developed in the specimen was continuously monitored. Half-value period of load, i.e. the time elapsed for the reduction of load to a half, was used as a measure of cross-linking, and it was significantly longer in 64 weeks old animals than in younger ones. This result corresponds well to the results of the elastic modulus of wall, indicating that higher wall stiffness in older arteries is attributable to the larger amount of stable collagen cross-linking. Then, the HIT method was applied to common carotid arteries from DOCA-salt hypertensive rats, and the results were compared with those from the age-matched, normotensive animals. Relative amount of matured cross-links showed a tendency of increasing by hypertension, which explains higher elastic modulus in hypertensive arteries than in normotensive ones.