Differences in collagen cross-linking between the four valves of the bovine heart: a possible role in adaptation to mechanical fatigue

Abstract

Hydrothermal isometric tension (HIT) testing and high-performance liquid chromatography were used to assess the molecular stability and cross-link population of collagen in the four valves of the adult bovine heart. Untreated and NaBH(4)-treated tissues under isometric tension were heated in a water bath to a 90 degrees C isotherm that was sustained for 5 h. The denaturation temperature (T(d)), associated with hydrogen bond rupture and molecular stability, and the half-time of load decay (t(1/2)), associated with peptide bond hydrolysis and intermolecular cross-linking, were calculated from acquired load/temperature/time data. An unpaired group of samples of the same population was biochemically assayed for the types and quantities of enzymatic cross-links present. Tissues known to endure higher in vivo transvalvular pressures had lower T(d) values, suggesting that molecular stability is inversely related to in vivo loading. The treated inflow valves (mitral and tricuspid) had significantly lower t(1/2) values than did treated outflow valves (aortic and pulmonary), suggesting lower overall cross-linking in the inflow valves. Inflow valves were also found to fail during HIT testing significantly more often than outflow valves, also suggestive of a decreased cross-link population. Inflow valves may be remodeling at a faster rate and may be at an earlier state of molecular "maturity" than outflow valves. At the molecular level, the thermal stability of collagen is associated with in vivo loading and may be influenced by the mature, aldimine-derived cross-link, histidinohydroxylysinonorleucine. We conclude that the valves of the heart utilize differing, location-specific strategies to resist biomechanical fatigue loading.

Development of a Simultaneous Cryo-Anchoring and Radiofrequency Ablation Catheter for Percutaneous Treatment of Mitral Valve Prolapse

“…2 Thus, we used 65°C as a threshold for permanent collagen denaturation and determined the area of tissue heated above this temperature. IR imaging reveals that while there is a distinct region of cryo-anchoring present through the full thickness of the leaflet, which stays relatively consistent across all RF energies, heating due to RF ablation dominates the leaflet temperature distribution.…”

Differential Changes in the Molecular Stability of Collagen from the Pulmonary and Aortic Valves During the Fetal-to-Neonatal Transition

“…1,11,25 Previous study in our laboratory with young adult bovine hearts has shown that the hydrothermal denaturation temperature, T d , of collagen from the four valves varies inversely with the maximum TVP expected for that valve: e.g., T d for pulmonary valves is significantly higher than that for aortic valves. 2 Whether or not these differences in molecular stability are a direct result of the differences in in vivo mechanical loading or due to some inherent differences in tissue structure from valve-to-valve is unknown. Nonetheless, the observation is intriguing.…”

Pregnancy-induced remodeling of heart valves

“…For instance, the inflow valves (mitral and tricuspid) arise solely from tissues of the endocardial cushions in the developing heart tube, whereas the outflow valves (aortic and pulmonary) are also derived from immigrating neural crest cells (5,12,20,22,47). On the other hand, higher transvalvular pressures (TVP) in the left side of the heart result in higher tensile stresses in the mitral and aortic valve leaflets (3,32). Therefore, the remodeling response to pregnancy may be valve specific.…”

“…For instance, Aldous et al (3) found that, valve to valve, collagen denaturation temperature was inversely correlated with increasing TVP. Furthermore, tissue from inflow valves contained significantly less mature and total cross-links compared with outflow valves.…”

“…Furthermore, tissue from inflow valves contained significantly less mature and total cross-links compared with outflow valves. This implied that the inflow valves had less mature collagen, which was due to perhaps faster remodeling than what oc-curred in the outflow valves (3). Studies from Merryman and colleagues (31,32) have correlated VIC phenotype and TVP.…”