Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice

J Biomech. 2022 Aug:141:111179. doi: 10.1016/j.jbiomech.2022.111179. Epub 2022 Jun 10.

Abstract

Mechanical homeostasis emerges following normal development of the arterial wall and requires thereafter a slow balanced degradation and deposition of extracellular matrix constituents within an unchanging mechanical state. Recent findings suggest that homeostasis is compromised in arterial aging, which contributes to the structural stiffening that is characteristic of aged central arteries. Matrix metalloproteinases (MMPs) have strong proteolytic activity and play fundamental roles in matrix turnover. Here, we use Mmp12-/- mice to examine effects of a potent metalloelastase, MMP-12, on the biomechanical phenotype of the thoracic and abdominal aorta in young and naturally aged mice. A key finding is that germline deletion of the gene (Mmp12) that encodes MMP-12 alters biomechanical properties from normal more in young adult than in older adult mice. Consequently, percent changes in biomechanical properties during aortic aging are greater in wild-type than in MMP-12 deficient mice, though with similar overall decreases in elastic energy storage and distensibility and increases in calculated pulse wave velocity. Reduced elastic energy storage compromises the ability of the aorta to augment antegrade and retrograde blood flow while an increased pulse wave velocity can adversely affect end organs, both conditions being characteristic of aortic aging in humans. In summary, MMP-12 is fundamental for establishing homeostatic values of biomechanical metrics in the aorta and its absence leads to a pre-aged aortic phenotype in young mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Animals
  • Aorta, Abdominal
  • Homeostasis
  • Humans
  • Matrix Metalloproteinase 12* / genetics
  • Matrix Metalloproteinases
  • Mice
  • Phenotype
  • Pulse Wave Analysis*
  • Young Adult

Substances

  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 12
  • matrix metallopeptidase 12, mouse