Jun N-terminal kinase inhibitor blocks angiogenesis by blocking VEGF secretion and an MMP pathway.
OBJECTIVE
The excessive proliferation and migration of vascular smooth muscle cells (SMCs) and angiogenesis of endothelial cells (ECs) participate in the growth and instability of atherosclerotic plaques. It is unclear whether Jun N-terminal kinase (JNK) is pro-or anti-atherogenic.


METHODS
We examined the direct effect of JNK inhibitor (JNK-I) on the proliferation and formation of tubes by human coronary SMCs and human coronary ECs.


RESULTS
Culture medium from JNK-I-treated SMCs prevented ECs from forming tubes in an in vitro model of angiogenesis indirectly by reducing the amount of vascular endothelial growth factor (VEGF) released from SMCs. In addition, JNK-I attenuated the expression of pro-matrix metalloproteinase-2 in ECs. When added back to the medium of SMCs treated with JNK-I, VEGF blocked the inhibitory effect on the formation of tubes.


CONCLUSIONS
Our results indicate JNK-I to have a direct anti-atherogenic effect in SMCs and ECs.
Miura
Shin-ichiro
S
Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Japan. miuras@cis.fukuoka-u.ac.jp
Matsuo
Yoshino
Y
Saku
Keijiro
K
D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D003331:Coronary Vessels / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology; D053505:Matrix Metalloproteinases, Secreted / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D048670:MAP Kinase Kinase 4; D053505:Matrix Metalloproteinases, Secreted