Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility

Matthew A Dale1, Melissa K Suh2, Shijia Zhao3

  • 1Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.

Atherosclerosis
|November 8, 2015
PubMed
Abstract

Insights

Genetic background significantly influences abdominal aortic aneurysm (AAA) development. The 129/SvEv mouse strain exhibits increased susceptibility to AAA compared to C57Bl/6 mice, linked to intrinsic aortic properties.

Area of Science:

  • Cardiovascular Research
  • Genetics and Disease
  • Atherosclerosis and Vascular Biology

Background:

  • Genetic background critically impacts cardiovascular phenotypes, as observed in Marfan syndrome murine models.
  • Variations in genetic background influence thoracic aortic aneurysm formation, rupture, and lifespan in mice.
  • C57Bl/6 mice show less susceptibility to thoracic aortic aneurysms than 129/SvEv mice.

Purpose of the Study:

  • To investigate the hypothesis that 129/SvEv mice exhibit increased susceptibility to abdominal aortic aneurysm (AAA) compared to C57Bl/6 mice.
  • To assess differences in aneurysm size, aortic tissue properties, immune response, and matrix metalloproteinase (MMP) expression between mouse strains.
  • To elucidate the role of intrinsic aortic properties in AAA susceptibility.

Main Methods:

  • Abdominal aortic aneurysm (AAA) was induced in C57Bl/6 and 129/SvEv mice via periaortic calcium chloride (CaCl2) application.
  • Measurements included baseline and post-induction aortic diameters, tissue elasticity, MMP expression (MMP-2, MMP-9), and immune cell infiltration (macrophages).
  • Bone marrow transplantation was performed to assess the role of myelogenous cells.

Main Results:

  • 129/SvEv mice developed significantly larger AAAs (83.0% increase) compared to C57Bl/6 mice (57.8% increase).
  • The aorta in 129/SvEv mice was stiffer (952.5 kPa) than in C57Bl/6 mice (621.4 kPa).
  • Elevated baseline MMP-2 and post-induction MMP-2 and MMP-9 levels, increased elastic lamella disruption, and greater macrophage infiltration were observed in 129/SvEv mice.

Conclusions:

  • 129/SvEv mice are demonstrably more susceptible to abdominal aortic aneurysm (AAA) than C57Bl/6 mice.
  • Intrinsic aortic properties, including baseline matrix metalloproteinase-2 (MMP-2) expression, contribute to AAA susceptibility.
  • Genetic background plays a crucial role in the development and severity of AAA.

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