Inhibition of cross-links in collagen is associated with reduced stiffness of the aorta in young rats.

Collagen and elastin fibres are of major importance in providing the aorta with tensile strength and elasticity. The presence of cross-links in collagen and elastin is essential for the mechanical stability of collagen and elastin fibres. beta-aminopropionitrile (BAPN) reduces the formation of cross-links by inhibiting the enzyme lysyloxidase. Young rats were injected with BAPN to inhibit the formation of cross-links, and the changes in the biomechanical and biochemical properties of the thoracic aorta were studied. The biomechanical analyses of aortic samples from BAPN-treated rats showed a significantly increased diameter (1.64 +/-0.02 mm), a significantly reduced maximum load (1.08+/-0.08 N), and a significantly reduced maximum stiffness (3.34+/-0.10 N) compared with controls (1.57+/-0.02 mm, 1.55+/-0.04 N and 4.49 +/-0.14 N, respectively). No changes in the concentrations of collagen and elastin were found. The content of pyridinoline, a mature collagen cross-link, was significantly decreased by 49% in the BAPN-treated group compared with controls. No changes in the concentration of desmosine + isodesmosine, the major cross-links of elastin. were found. The present study shows that cross-links are essential in providing mechanical stability of the aorta. Even a partial inhibition of the cross-linking processes results in a destabilisation of the aortic wall with increased diameter and reduced strength and stiffness.