Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm

Paul D. Dimusto, Guanyi Lu, Abhijit Ghosh, Karen J. Roelofs, Omar Sadiq, Brendan McEvoy, Gang Su, Adriana Laser, Castigliano Bhamidipati, Gorav Ailawadi, Peter K. Henke, Jonathan L. Eliason, Gilbert R. Upchurch

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: In humans, there is a 4:1 male:female ratio in the incidence of abdominal aortic aneurysms (AAAs). c-Jun-N-terminal kinase (JNK) is an important upstream regulator of several enzymes involved in AAA formation, including the matrix metalloproteinases (MMPs). The purpose of this study was to determine if there is a gender difference between males and females in JNK during AAA formation. Materials and Methods: Male and female C57/B6 mice underwent aortic perfusion with elastase or heat inactivated elastase with aortas harvested at d 3 and 14 for phenotype determination, RT-PCR, Western blot, and zymography. Additionally, in vitro experiments using siRNA were conducted to define JNK regulation of matrix metalloproteinases (MMPs). A t-test was used to compare between groups. Results: Males formed larger AAAs at d 14 compared with females (P < 0.001), with significantly higher levels of JNK1 protein, proMMP9, proMMP2, and active MMP2. At d 3, males had more JNK1 mRNA, protein, and MMP activity. Knockdown of JNK 1 or 2 in vitro decreased MMP activity, while knockdown of JNK 1 and 2 together blocked all MMP activity. Conclusion: Alterations in JNK between genders is partially responsible for the differential rates of experimental AAA formation, likely through differential regulation of MMPs.

Original languageEnglish (US)
Pages (from-to)687-695
Number of pages9
JournalJournal of Surgical Research
Volume176
Issue number2
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

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JNK Mitogen-Activated Protein Kinases
Abdominal Aortic Aneurysm
Matrix Metalloproteinases
Rodentia
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinase 8
Pancreatic Elastase
Small Interfering RNA
Aorta
Proteins
Perfusion
Hot Temperature
Western Blotting
Phenotype
Polymerase Chain Reaction
Messenger RNA
Incidence
Enzymes

Keywords

  • abdominal aortic aneurysm
  • elastase model
  • gender
  • JNK
  • rodent

ASJC Scopus subject areas

  • Surgery

Cite this

Dimusto, P. D., Lu, G., Ghosh, A., Roelofs, K. J., Sadiq, O., McEvoy, B., ... Upchurch, G. R. (2012). Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm. Journal of Surgical Research, 176(2), 687-695. https://doi.org/10.1016/j.jss.2011.11.1024

Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm. / Dimusto, Paul D.; Lu, Guanyi; Ghosh, Abhijit; Roelofs, Karen J.; Sadiq, Omar; McEvoy, Brendan; Su, Gang; Laser, Adriana; Bhamidipati, Castigliano; Ailawadi, Gorav; Henke, Peter K.; Eliason, Jonathan L.; Upchurch, Gilbert R.

In: Journal of Surgical Research, Vol. 176, No. 2, 01.08.2012, p. 687-695.

Research output: Contribution to journalArticle

Dimusto, PD, Lu, G, Ghosh, A, Roelofs, KJ, Sadiq, O, McEvoy, B, Su, G, Laser, A, Bhamidipati, C, Ailawadi, G, Henke, PK, Eliason, JL & Upchurch, GR 2012, 'Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm', Journal of Surgical Research, vol. 176, no. 2, pp. 687-695. https://doi.org/10.1016/j.jss.2011.11.1024
Dimusto, Paul D. ; Lu, Guanyi ; Ghosh, Abhijit ; Roelofs, Karen J. ; Sadiq, Omar ; McEvoy, Brendan ; Su, Gang ; Laser, Adriana ; Bhamidipati, Castigliano ; Ailawadi, Gorav ; Henke, Peter K. ; Eliason, Jonathan L. ; Upchurch, Gilbert R. / Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm. In: Journal of Surgical Research. 2012 ; Vol. 176, No. 2. pp. 687-695.
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abstract = "Background: In humans, there is a 4:1 male:female ratio in the incidence of abdominal aortic aneurysms (AAAs). c-Jun-N-terminal kinase (JNK) is an important upstream regulator of several enzymes involved in AAA formation, including the matrix metalloproteinases (MMPs). The purpose of this study was to determine if there is a gender difference between males and females in JNK during AAA formation. Materials and Methods: Male and female C57/B6 mice underwent aortic perfusion with elastase or heat inactivated elastase with aortas harvested at d 3 and 14 for phenotype determination, RT-PCR, Western blot, and zymography. Additionally, in vitro experiments using siRNA were conducted to define JNK regulation of matrix metalloproteinases (MMPs). A t-test was used to compare between groups. Results: Males formed larger AAAs at d 14 compared with females (P < 0.001), with significantly higher levels of JNK1 protein, proMMP9, proMMP2, and active MMP2. At d 3, males had more JNK1 mRNA, protein, and MMP activity. Knockdown of JNK 1 or 2 in vitro decreased MMP activity, while knockdown of JNK 1 and 2 together blocked all MMP activity. Conclusion: Alterations in JNK between genders is partially responsible for the differential rates of experimental AAA formation, likely through differential regulation of MMPs.",
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T1 - Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm

AU - Dimusto, Paul D.

AU - Lu, Guanyi

AU - Ghosh, Abhijit

AU - Roelofs, Karen J.

AU - Sadiq, Omar

AU - McEvoy, Brendan

AU - Su, Gang

AU - Laser, Adriana

AU - Bhamidipati, Castigliano

AU - Ailawadi, Gorav

AU - Henke, Peter K.

AU - Eliason, Jonathan L.

AU - Upchurch, Gilbert R.

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N2 - Background: In humans, there is a 4:1 male:female ratio in the incidence of abdominal aortic aneurysms (AAAs). c-Jun-N-terminal kinase (JNK) is an important upstream regulator of several enzymes involved in AAA formation, including the matrix metalloproteinases (MMPs). The purpose of this study was to determine if there is a gender difference between males and females in JNK during AAA formation. Materials and Methods: Male and female C57/B6 mice underwent aortic perfusion with elastase or heat inactivated elastase with aortas harvested at d 3 and 14 for phenotype determination, RT-PCR, Western blot, and zymography. Additionally, in vitro experiments using siRNA were conducted to define JNK regulation of matrix metalloproteinases (MMPs). A t-test was used to compare between groups. Results: Males formed larger AAAs at d 14 compared with females (P < 0.001), with significantly higher levels of JNK1 protein, proMMP9, proMMP2, and active MMP2. At d 3, males had more JNK1 mRNA, protein, and MMP activity. Knockdown of JNK 1 or 2 in vitro decreased MMP activity, while knockdown of JNK 1 and 2 together blocked all MMP activity. Conclusion: Alterations in JNK between genders is partially responsible for the differential rates of experimental AAA formation, likely through differential regulation of MMPs.

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