MMP-12 has a role in abdominal aortic aneurysms in mice

G Matthew Longo, Steven J. Buda, Nicola Fiotta, Wanfen Xiong, Timothy Griener, Steven Shapiro, Bernard Timothy Baxter

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Background. Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. Methods. A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl2) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12-/-) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. Results. There is an increase of 63 ± 5% (mean ± SEM) in aortic diameters of WT mice after CaCl2 inductions, while MMP-12-/- mice increased only 26 ± 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12-/-mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl2 treatment, whereas no MMP-12 was detected in MMP-12-/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12-/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. Conclusions. MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.

Original languageEnglish (US)
Pages (from-to)457-462
Number of pages6
JournalSurgery
Volume137
Issue number4
DOIs
StatePublished - Apr 2005

Fingerprint

Matrix Metalloproteinase 12
Abdominal Aortic Aneurysm
Aneurysm
Aorta
Matrix Metalloproteinase 2
Macrophages
Matrix Metalloproteinase 9
Calcium Chloride
Elastic Tissue
Gelatin
Caseins

ASJC Scopus subject areas

  • Surgery

Cite this

MMP-12 has a role in abdominal aortic aneurysms in mice. / Longo, G Matthew; Buda, Steven J.; Fiotta, Nicola; Xiong, Wanfen; Griener, Timothy; Shapiro, Steven; Baxter, Bernard Timothy.

In: Surgery, Vol. 137, No. 4, 04.2005, p. 457-462.

Research output: Contribution to journalArticle

Longo, G Matthew ; Buda, Steven J. ; Fiotta, Nicola ; Xiong, Wanfen ; Griener, Timothy ; Shapiro, Steven ; Baxter, Bernard Timothy. / MMP-12 has a role in abdominal aortic aneurysms in mice. In: Surgery. 2005 ; Vol. 137, No. 4. pp. 457-462.
@article{5bcfd83e268148859d1e9071f92a644e,
title = "MMP-12 has a role in abdominal aortic aneurysms in mice",
abstract = "Background. Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. Methods. A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl2) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12-/-) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. Results. There is an increase of 63 ± 5{\%} (mean ± SEM) in aortic diameters of WT mice after CaCl2 inductions, while MMP-12-/- mice increased only 26 ± 14{\%}. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12-/-mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl2 treatment, whereas no MMP-12 was detected in MMP-12-/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12-/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. Conclusions. MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.",
author = "Longo, {G Matthew} and Buda, {Steven J.} and Nicola Fiotta and Wanfen Xiong and Timothy Griener and Steven Shapiro and Baxter, {Bernard Timothy}",
year = "2005",
month = "4",
doi = "10.1016/j.surg.2004.12.004",
language = "English (US)",
volume = "137",
pages = "457--462",
journal = "Surgery (United States)",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - MMP-12 has a role in abdominal aortic aneurysms in mice

AU - Longo, G Matthew

AU - Buda, Steven J.

AU - Fiotta, Nicola

AU - Xiong, Wanfen

AU - Griener, Timothy

AU - Shapiro, Steven

AU - Baxter, Bernard Timothy

PY - 2005/4

Y1 - 2005/4

N2 - Background. Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. Methods. A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl2) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12-/-) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. Results. There is an increase of 63 ± 5% (mean ± SEM) in aortic diameters of WT mice after CaCl2 inductions, while MMP-12-/- mice increased only 26 ± 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12-/-mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl2 treatment, whereas no MMP-12 was detected in MMP-12-/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12-/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. Conclusions. MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.

AB - Background. Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. Methods. A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl2) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12-/-) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. Results. There is an increase of 63 ± 5% (mean ± SEM) in aortic diameters of WT mice after CaCl2 inductions, while MMP-12-/- mice increased only 26 ± 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12-/-mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl2 treatment, whereas no MMP-12 was detected in MMP-12-/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12-/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. Conclusions. MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.

UR - http://www.scopus.com/inward/record.url?scp=15944415451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15944415451&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2004.12.004

DO - 10.1016/j.surg.2004.12.004

M3 - Article

C2 - 15800495

AN - SCOPUS:15944415451

VL - 137

SP - 457

EP - 462

JO - Surgery (United States)

JF - Surgery (United States)

SN - 0039-6060

IS - 4

ER -