Background

Pulmonary arterial hypertension (PAH) results in proximal pulmonary artery remodeling, which includes deposition of elastin and collagen. We have previously studied the role of elastin in this remodeling process through purification; however, collagen cannot be purified separately. Here we use materials modeling to predict the behavior of collagen under normotensive and hypertensive conditions using experimental data from an animal model of the developing lung circulation.

Methods and results

Rectangular samples from fresh main, left and right pulmonary arteries (MPA, LPA, and RPA) of neonatal calves in both circumferential and longitudinal directions were prepared for uniaxial tensile test. A one-layer, homogeneous model is considered for PAs and a strain-energy density function composed of the neo-Hookean model and the Fung-type exponential form is used to characterize the passive elastic behavior of PAs. The Fung-type exponential function, representing the orthotropic contribution, is utilized to describe collagen.

This strain-energy density function was found to fit very well to the experimental data. The model predicts that collagen in LPA and RPA, but not in MPA, increases the modulus in circumferential direction significantly from control to hypoxic state by more than 56% and 87% at strain levels of 0.3 and 0.6 respectively; collagen in the three PAs does not change significantly in the longitudinal direction. The contribution of collagen to the arterial circumferential modulus exhibited no significant change from control to hypoxic groups for three PAs (P>0.05). For both groups, collagen carries less than 50% of the overall mechanical load at low circumferential strain 0.3, but becomes the dominant load-carrying component at high circumferential strain (> 0.6). We also found that the percentage of physiological pressure carried by collagen increases by more than 50% and 15% at diastole and systole, respectively.

Conclusions

Our study predicts that collagen in LPA and RPA, but not in MPA, becomes stiffer as a result of PAH; such a change is possibly due to increased collagen cross-linking. The contribution of collagen to the arterial circumferential modulus does not change significantly from control to hypoxic state, implying that non-collagenous material also increase stiffness due to PAH. Finally, collagen is found to carry a greater pressure load in the hypoxic state.