The effects of pulmonary hypertension on the mechanical properties of arteries in Cav-1-/- mice

Pulmonary hypertension (PH) is a complex disorder characterized by an increase in pulmonary artery pressure ultimately leading to right heart failure. Hypertensive pressures result in proximal artery stiffening which contributes to an increased ventricular afterload and right ventricular hypertrophy. Recently, the generation of Cav-1 deficient mice (Cav-1-/-) has provided an alternative genetic model to study the effects of pulmonary hypertension on the vasculature. To determine the effects of hypertension on the systemic and pulmonary circulation, pulmonary and carotid arteries of Cav-1-/- mice were mechanically tested and compared to their normal counterpart. Mice at 4-6 and 9-12 months of age were studied in order to evaluate vascular changes in Cav-1-/- mice during the onset of disease and at the approximate time of heart failure respectively. Mechanical tests revealed increases in both pulmonary and carotid artery stiffness at 4-6 months. Increases in stiffness were quantified by a decrease in circumferential stretch and transition strain, increases in elastic moduli, and an increase in total strain energy when evaluated at normal biaxial strains. Changes in mechanical properties at 4-6 months had significant correlations with changes in collagen and elastin thickness (percent protein multiplied by wall thickness). No further increase in either pulmonary or carotid artery stiffness was found at 9-12 months. These results provide the first insight into the mechanical and structural changes in the vasculature as a result of Cav-1-/- induced pulmonary hypertension. This information will be critical in describing the effects of artery remodeling as it contributes to ventricular failure in PH.