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

Bart Spronck; Abhay B. Ramachandra; Jakub Toczek; Jinah Han; Mehran Sadeghi; Jay D. Humphrey

doi:10.1016/j.artres.2018.10.024

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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.2018.10.024 How 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.
Open Access: This is an open access article distributed under the CC BY-NC license.

References

1.SL Liu, YH Bae, C Yu, J Monslow, EA Hawthorne, P Castagnino, E Branchetti, G Ferrari, SM Damrauer, E Pure, and RK Assoian, Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening, Sci Rep, Vol. 5, 2015, pp. 17189.

2.J Ferruzzi, MR Bersi, and JD Humphrey, Biomechanical phenotyping of central arteries in health and disease: advantages of and Methods: for murine models, Ann Biomed Eng, Vol. 41, 2013, pp. 1311-1330.

3.J Ferruzzi, D Madziva, AW Caulk, G Tellides, and JD Humphrey, Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences, Biomech Model Mechanobiol, 2018. [in press]

4.J Ferruzzi, MR Bersi, S Uman, H Yanagisawa, and JD Humphrey, Decreased elastic energy storage, not increased material stiffness, characterizes central artery dysfunction in fibulin-5 deficiency independent of sex, J Biomech Eng, 2015, pp. 137.

5.J Ferruzzi, MR Bersi, RP Mecham, F Ramirez, H Yanagisawa, G Tellides, and JD Humphrey, Loss of Elastic Fiber Integrity Compromises Common Carotid Artery Function: Implications for Vascular Aging, Artery Res, Vol. 14, 2016, pp. 41-52.

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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.2018.10.024 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC license.

Cite this article

ris enw bib

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  -

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