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2.1 Knock-Out of Matrix Metalloproteinase-12 Exacerbates Compromised Mechanical Homeostasis in Arterial Aging
Artery Research volume 24, page 69 (2018)
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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Spronck, B., Ramachandra, A.B., Toczek, J. et al. 2.1 Knock-Out of Matrix Metalloproteinase-12 Exacerbates Compromised Mechanical Homeostasis in Arterial Aging. Artery Res 24, 69 (2018). https://doi.org/10.1016/j.artres.2018.10.024
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DOI: https://doi.org/10.1016/j.artres.2018.10.024