Telmisartan-enhanced hypercholesterolaemic serum-induced vascular endothelial growth factor expression in immortalized human umbilical vascular endothelial cells.
OBJECTIVE
To clarify whether hypercholesterolaemia can increase vascular endothelial growth factor (VEGF) expression in human umbilical vascular endothelial cells (HUVECs) through the phosphatidylinositol 3-kinase (PI3K) pathway, and whether a special angiotensin II receptor blocker, telmisartan, can attenuate VEGF expression induced by hypercholesterolaemia.


METHODS
Levels of VEGF expression, PI3K activity and angiogenesis in vitro were determined by various methods after HUVECs were incubated with hypercholesterolaemic serum or combined with telmisartan and/or wortmannin.


RESULTS
We found that hypercholesterolaemic serum (cholesterol > or = 0.08 mmol/L) can increase VEGF expression in HUVECs and that telmisartan cooperates with hypercholesterolaemic serum in promoting VEGF expression. The increased VEGF expression was associated with enhanced PI3K activity and could be significantly inhibited by wortmannin, a potent PI3K inhibitor. Likewise, hypercholesterolaemic serum significantly promoted angiogenesis in vitro, which could be inhibited when PI3K activity was suppressed.


CONCLUSIONS
Our study suggests that hypercholesterolaemic serum induces VEGF expression through PI3K in HUVECs and that telmisartan cooperates with hypercholesterolaemia in promoting VEGF expression.
Bian
C
C
Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Lin
J
J
Li
X C
XC
Wang
Y F
YF
Hu
H Q
HQ
Chen
P
P
D000730:Androstadienes / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D000077333:Telmisartan; D014472:Umbilicus / Q000098:blood supply*; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D000077191:Wortmannin
D000730:Androstadienes; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077333:Telmisartan; D042461:Vascular Endothelial Growth Factor A; D000077191:Wortmannin