Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 Mitogen-Activated Protein Kinase

Rationale:Aortic stiffening commonly occurs in hypertension and further elevates systolic pressure. Hypertension is also associated with vascular inflammation and increased mechanical stretch. The interplay between inflammation, mechanical stretch, and aortic stiffening in hypertension remains undefined. Objective:Our aim was to determine the role of inflammation and mechanical stretch in aortic stiffening. Methods and Results:Chronic angiotensin II infusion caused marked aortic adventitial collagen deposition, as quantified by Masson trichrome blue staining and biochemically by hydroxyproline content, in wild-type but not in recombination activating gene-1–deficient mice. Aortic compliance, defined by ex vivo measurements of stress–strain curves, was reduced by chronic angiotensin II infusion in wild-type mice (P<0.01) but not in recombination activating gene-1–deficient mice (P<0.05). Adoptive transfer of T-cells to recombination activating gene-1–deficient mice restored aortic collagen deposition and s...