title: Excessive Adventitial Remodeling Leads to Early Aortic Maladaptation in Angiotensin-Induced Hypertension.
abstract: The primary function of central arteries is to store elastic energy during systole and to use it to sustain blood flow during diastole. Arterial stiffening compromises this normal mechanical function and adversely affects end organs, such as the brain, heart, and kidneys. Using an angiotensin II infusion model of hypertension in wild-type mice, we show that the thoracic aorta exhibits a dramatic loss of energy storage within 2 weeks that persists for at least 4 weeks. This diminished mechanical functionality results from increased structural stiffening as a result of an excessive accumulation of adventitial collagen, not a change in the intrinsic stiffness of the wall. A detailed analysis of the transmural biaxial wall stress suggests that the exuberant production of collagen results more from an inflammatory response than from a mechano-adaptation, hence reinforcing the need to control inflammation, not just blood pressure. Although most clinical assessments of arterial stiffening focus on intimal-medial thickening, these results suggest a need to measure and control the highly active and important adventitia.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT.
authors.forename: Mathew R
authors.initials: MR
authors.lastname: Bersi
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellini
authors.affiliation: Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: Kim R C
authors.initials: KRC
authors.lastname: Montaniel
authors.affiliation: Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN.
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT.|Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Humphrey
mesh_terms: D063194:Adventitia / Q000187:drug effects / Q000473:pathology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013312:Stress, Physiological; D066253:Vascular Remodeling / Q000187:drug effects / Q000502:physiology; D059289:Vascular Stiffness / Q000187:drug effects / Q000502:physiology*
chemical_list: D000804:Angiotensin II
keywords: arterial stiffness; collagen; elastic energy; hypertension; wall stress