Soluble form of vascular cell adhesion molecule 1 induces migration and proliferation of vascular smooth muscle cells.
BACKGROUND
Serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1) shed from its membrane-bound form are elevated in hypertension. This study clarified the effects of sVCAM-1 on vascular responses in rat aortic smooth muscle cells (RASMCs).


METHODS
Boyden chamber, 5-bromo-2'-deoxyuridine incorporation and ex vivo aortic ring assays for migration and proliferation, and Western blot for the kinase activity were used.


RESULTS
Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were compared functionally. sVCAM-1 increased RASMC migration and proliferation, which were greater in SHR compared with WKY rats. RASMCs expressed the very late antigen 4alpha receptor integrin with no difference between SHR and WKY rats. Inhibitors of phosphoinositide kinase 3 (PI3K) and spleen tyrosine kinase (Syk) and small interference RNA-Syk abolished the sVCAM-1-induced migration, proliferation and phosphorylation of focal adhesion kinase. The phosphorylation of Syk was significantly greater in RASMCs from SHR than from WKY rats. sVCAM-1 increased aortic sprout outgrowth, which was inhibited by inhibitors of PI3K and Syk.


CONCLUSIONS
This study suggests that sVCAM-1 promotes the RASMC migration and proliferation via the focal adhesion kinase pathway regulated by Syk and PI3K, and the altered sVCAM-1-induced responses during hypertension are closely associated with the increments in intracellular signal transmission.
Lee
Hwan Myung
HM
Department of Medicine, College of Medicine, Konkuk University, Chungju, South Korea.
Kim
Hyo Jin
HJ
Won
Kyung-Jong
KJ
Choi
Wahn Soo
WS
Park
Seung Hwa
SH
Song
Hyuk
H
Park
Pyo-Jam
PJ
Park
Tae-Kyu
TK
Lee
Chang-Kwon
CK
Kim
Bokyung
B
D000818:Animals; D001011:Aorta / Q000254:growth & development; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006128:Growth / Q000187:drug effects; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D019010:Vascular Cell Adhesion Molecule-1