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


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.


CONCLUSIONS
Alterations in JNK between genders is partially responsible for the differential rates of experimental AAA formation, likely through differential regulation of MMPs.
Jobst Vascular Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA.
Paul D
PD
DiMusto
Guanyi
G
Lu
Abhijit
A
Ghosh
Karen J
KJ
Roelofs
Omar
O
Sadiq
Brendan
B
McEvoy
Gang
G
Su
Adriana
A
Laser
Castigliano M
CM
Bhamidipati
Gorav
G
Ailawadi
Peter K
PK
Henke
Jonathan L
JL
Eliason
Gilbert R
GR
Upchurch
D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology / Q000201:enzymology*; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010196:Pancreatic Elastase / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D012727:Sex Characteristics
D034741:RNA, Small Interfering; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D010196:Pancreatic Elastase; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse