2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING
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 a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | Artery Research |
| Online Access: | https://www.atlantis-press.com/article/125929973/view |
| _version_ | 1811234213511299072 |
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| author | Bart Spronck Abhay B. Ramachandra Jakub Toczek Jinah Han Mehran Sadeghi Jay D. Humphrey |
| author_facet | Bart Spronck Abhay B. Ramachandra Jakub Toczek Jinah Han Mehran Sadeghi Jay D. Humphrey |
| author_sort | Bart Spronck |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T11:32:55Z |
| format | Article |
| id | doaj.art-40aa15f67ff049cfa694ce50b7104b9e |
| institution | Directory Open Access Journal |
| issn | 1876-4401 |
| language | English |
| last_indexed | 2024-04-12T11:32:55Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Artery Research |
| spelling | doaj.art-40aa15f67ff049cfa694ce50b7104b9e2022-12-22T03:34:57ZengBMCArtery Research1876-44012018-12-012410.1016/j.artres.2018.10.0242.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGINGBart SpronckAbhay B. RamachandraJakub ToczekJinah HanMehran SadeghiJay D. HumphreyBackground: 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.https://www.atlantis-press.com/article/125929973/view |
| spellingShingle | Bart Spronck Abhay B. Ramachandra Jakub Toczek Jinah Han Mehran Sadeghi Jay D. Humphrey 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING Artery Research |
| title | 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING |
| title_full | 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING |
| title_fullStr | 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING |
| title_full_unstemmed | 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING |
| title_short | 2.1 KNOCK-OUT OF MATRIX METALLOPROTEINASE-12 EXACERBATES COMPROMISED MECHANICAL HOMEOSTASIS IN ARTERIAL AGING |
| title_sort | 2 1 knock out of matrix metalloproteinase 12 exacerbates compromised mechanical homeostasis in arterial aging |
| url | https://www.atlantis-press.com/article/125929973/view |
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