Artery Research

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Volume 24, Issue C, December 2018, Pages 69 - 69

2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING

Authors
Bart Spronck1, Abhay B. Ramachandra1, Jakub Toczek2, 3, 4, Jinah Han2, 3, 4, Mehran Sadeghi2, 3, 4, Jay D. Humphrey1, 5
1Department of Biomedical Engineering, Yale University, New Haven, CT, USA
2Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, CT, USA
3Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
4Yale Cardiovascular Research Center, New Haven, CT, USA
5Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT, USA
Available Online 4 December 2018.
DOI
10.1016/j.artres.2018.10.024How to use a DOI?
Abstract

Background: Matrix metalloproteinase-12 (MMP12) may modulate arterial stiffening with age [1]. We aimed to study the effect of aging on biaxial arterial stiffness in wild-type (WT) and MMP12 knock-out (MMP12-/-) mice.

Methods and Results: After euthanasia, descending thoracic (DTA) and suprarenal abdominal (SAA) aortas of young and old, WT (ages 21 ± 0 and 103 ± 1 weeks; mean ± SE) and MMP12-/- (13 ± 0 and 52 ± 0 weeks) male mice were dissected and cannulated on glass pipettes in a computer-controlled biaxial testing device. Pressure-diameter tests were performed at 95%/100%/105% of estimated in vivo stretch; axial force-length tests at pressures of 10/60/100/140 mmHg. Data were fitted using a four-fiber constitutive model [2]. WT and MMP12-/- blood pressures were comparable (133/88 vs. 126/93 mmHg; SBP/DBP; telemetry); WT aging did not influence blood pressure [3]. All metrics are therefore presented at a common pressure (figure). At first sight, MMP12-/- aging resembles WT aging: increased wall thickness (figure, panel A) leading to decreased circumferential stress (B) and decreased stored strain energy (C) [3–5]. However, in WT aging, circumferential material stiffness decreased, which did not occur in MMP12-/- (D). Structural stiffness and pulse wave velocity remained constant in WT mice but increased in MMP12-/- (E-F).

Discussion: Our findings suggest that in both WT and MMP12-/-, mechanical homeostasis with aging was compromised, a finding that was exacerbated with MMP12-/-. MMP12-/- was previously reported to reduce age-associated stiffening [1]. This contradictory finding may be explained by the use of atomic force microscopy in [1] (measuring compressive stiffness) versus our use of tensile biaxial testing.

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<Previous Article In Issue
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Journal
Artery Research
Volume-Issue
24 - C
Pages
69 - 69
Publication Date
2018/12/04
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2018.10.024How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

risenwbib
TY  - JOUR
AU  - Bart Spronck
AU  - Abhay B. Ramachandra
AU  - Jakub Toczek
AU  - Jinah Han
AU  - Mehran Sadeghi
AU  - Jay D. Humphrey
PY  - 2018
DA  - 2018/12/04
TI  - 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING
JO  - Artery Research
SP  - 69
EP  - 69
VL  - 24
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2018.10.024
DO  - 10.1016/j.artres.2018.10.024
ID  - Spronck2018
ER  -