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

被引：30

作者：

Dale, Matthew A. ^{[1
,4
]}

Suh, Melissa K. ^{[1
]}

Zhao, Shijia ^{[2
]}

Meisinger, Trevor ^{[1
]}

Gu, Linxia ^{[2
]}

Swier, Vicki J. ^{[3
]}

Agrawal, Devendra K. ^{[3
]}

Greiner, Timothy C. ^{[4
]}

Carson, Jeffrey S. ^{[1
]}

Baxter, B. Timothy ^{[1
,4
]}

Xiong, Wanfen ^{[1
]}

机构：

[1] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68198 USA

[2] Univ Nebraska, Dept Mech & Mat Engn, Lincoln, NE USA

[3] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA

[4] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

来源：

ATHEROSCLEROSIS | 2015年 / 243卷 / 02期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Aneurysm; Matrix metalloproteinase; Aorta; MOUSE STRAIN DIFFERENCES; ELASTIN; DEFICIENCY; DISEASE; PHENOTYPE; RUPTURE; LESIONS; MATRIX; CANCER; MODEL;

D O I：

10.1016/j.atherosclerosis.2015.10.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression. Methods: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured. Results: Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% +/- 13.6 increase compared to 57.8% +/- 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa +/- 93.6 versus 621.4 kPa +/- 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size. Conclusions: These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：621 / 629

页数：9

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