Severe pulmonary arterial hypertension induced by hypoxia and SU5416 in mice increased structural stiffness and decreased damping ratio in large pulmonary arteries at a physiological frequency of 10 Hz.
Does chronic hypoxia combined with SU5416 alter the frequency-dependent viscoelastic properties of large pulmonary arteries in mice?
In a mouse model of severe pulmonary arterial hypertension, large pulmonary arteries exhibit increased structural stiffness and decreased damping capacity at physiological frequencies, driven by extracellular matrix changes rather than smooth muscle contraction.
p-value: p=<0.05
Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation.
Wang et al. (Wed,) conducted a other in Pulmonary arterial hypertension (n=12). Hypoxia and SU5416 vs. Normoxia was evaluated on Dynamic structural stiffness (k) and damping ratio (D) at 10 Hz (p=<0.05). Severe pulmonary arterial hypertension induced by hypoxia and SU5416 in mice increased structural stiffness and decreased damping ratio in large pulmonary arteries at a physiological frequency of 10 Hz.