TY - JOUR
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 M.
AU - Ailawadi, Gorav
AU - Henke, Peter K.
AU - Eliason, Jonathan L.
AU - Upchurch, Gilbert R.
N1 - Funding Information:
The authors thank Mr. Chris Hedly for graphic design assistance in creating the figures for this manuscript. This work was supported by NIH R01 HL081629-01 (GRU), NIH R01 HL081629-03S1 (GRU), Coller Society Research Fellowship (PDD), and the University of Michigan Aortic Research Fellowship (PDD).
PY - 2012/8
Y1 - 2012/8
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.
AB - 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.
KW - JNK
KW - abdominal aortic aneurysm
KW - elastase model
KW - gender
KW - rodent
UR - http://www.scopus.com/inward/record.url?scp=84863984453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863984453&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2011.11.1024
DO - 10.1016/j.jss.2011.11.1024
M3 - Article
C2 - 22316675
AN - SCOPUS:84863984453
SN - 0022-4804
VL - 176
SP - 687
EP - 695
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -