Arterial Wall Stiffening in Caveolin-1 Deficiency-Induced Pulmonary Artery Hypertension in Mice.

Abstract

Pulmonary artery hypertension (PAH) is a complex disorder that can lead to right heart failure. The generation of caveolin-1 deficient mice (CAV-1-/-) has provided an alternative genetic model to study the mechanisms of pulmonary hypertension. However, the vascular adaptations in these mice have not been characterized. To determine the histological and functional changes in the pulmonary and carotid arteries in CAV-1-/- induced PAH. Pulmonary and carotid arteries of young (4-6 months old) and mature (9-12 months old) CAV-1-/- mice were tested and compared to normal wild type mice. Artery stiffness increases in CAV-1-/- mice, especially the circumferential stiffness of the pulmonary arteries. 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 at physiologic strains. Changes in mechanical properties for the pulmonary artery correlated with increased collagen content while carotid artery mechanical properties correlated with decreased elastin content. We demonstrated that an increase in artery stiffness is associated with CAV-1 deficiency-induced pulmonary hypertension. These results improve our understanding of artery remodeling in PAH.