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