2.2 Modest Region-Specific, Sex-Independent Aortic Remodelling when Hypertension is Superimposed on Aging

DOI

10.2991/artres.k.191224.007How to use a DOI?

Abstract

Background: Aging and hypertension often co-occur, which complicates distinguishing their biomechanical effects on arteries clinically. While aortic elastin (half-life ~70 years) is reduced in human aging, in mouse aging (lifespan ~2 years) it remains mostly intact. Knock-out of elastin-associated glycoprotein fibulin-5 (Fbln5^−/−) in mice however yields a biomechanical phenotype that resembles human aging.

Methods: Adult male and female Fbln5^+/+ and Fbln5^−/− mice were studied under three conditions: untreated, after 14-day 490 ng/kg/min angiotensin-II infusion (AngII), and after 13 weeks on 8%-NaCl chow + 3 g/L L-NAME drinking water (L-NAME-NaCl). After tail-cuff blood pressure (BP) measurement and euthanasia, descending thoracic (DTA) and infrarenal abdominal (IAA) aortas were dissected and tested using a computer-controlled biaxial testing device.

Results: Salt+L-NAME led to adaptive remodelling (circumferential stress homeostasis) and maladaptive remodelling (lack thereof) in the IAA and DTA, respectively (figure, males), while AngII caused luminal dilatation but little remodelling of the wall. Effects of aging (Fbln5^−/−) were more dramatic than those due to induced hypertension. Consequently, superimposing hypertension on aging led to modest additional changes in luminal radius and wall thickness, though increased stress and stiffness metrics due to increased pressure loading of the wall [3] Trends in females were similar to those in males.

Conclusions: Effects of hypertension on aortic remodelling are modest when superimposed on aging in mice. These findings are consistent with general observations in humans [4,5], though separated here for the first time in a rodent model characterized by a severe loss of elastic fiber integrity similar to that found in the aged human aorta.

Copyright

© 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Bart Spronck
AU  - Jacopo Ferruzzi
AU  - Alexander W. Caulk
AU  - Sae-Il Murtada
AU  - Jay D. Humphrey
PY  - 2020
DA  - 2020/02/15
TI  - 2.2 Modest Region-Specific, Sex-Independent Aortic Remodelling when Hypertension is Superimposed on Aging
JO  - Artery Research
SP  - S8
EP  - S9
VL  - 25
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191224.007
DO  - 10.2991/artres.k.191224.007
ID  - Spronck2020
ER  -