Atorvastatin completely inhibits VEGF-induced ACE upregulation in human endothelial cells

Angiotensin-converting enzyme (ACE) plays an important role in the pathophysiology of cardiovascular disease. We investigated whether atorvastatin, a powerful agent for the prevention and treatment of cardiovascular disease, influences ACE production in endothelial cells. Human umbilical cord vein endothelial cells were treated with VEGF (476 pM), which induced ACE upregulation. Cotreatment with atorvastatin (0.1–10 μM) dose dependently inhibited VEGF-induced ACE upregulation. In the presence of mevalonate (100 μM), atorvastatin failed to downregulate VEGF-induced ACE production. Cotreatment of the cells with either farnesylpyrophosphate (FPP; 5 μM) or geranylgeranylpyrophosphate (GGPP; 5 μM) partially inhibited the suppressive effect of atorvastatin. Pretreatment of the cells with Rho-associated protein kinase inhibitor, Y-27632 (10 μM), partially inhibited VEGF-induced ACE upregulation. VEGF (476 pM) caused PKC phosphorylation, which was inhibited by cotreatment of the cells with atorvastatin. Atorvastatin inhibited VEGF-induced ACE upregulation probably by inhibiting PKC phosphorylation. This effect was mediated via inhibition of the mevalonate pathway. ACE downregulation may be an additional beneficial effect of statins in the treatment of cardiovascular disease.

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Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism

Journal of Cellular Biochemistry ◽

10.1002/jcb.20963 ◽

2006 ◽

Vol 99 (4) ◽

pp. 1216-1232 ◽

Cited By ~ 63

Author(s):

Chi Iou Lin ◽

Chiung-Nien Chen ◽

Jiun Hong Chen ◽

Hsinyu Lee

Keyword(s):

Endothelial Cells ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Umbilical Cord Vein ◽

Human Umbilical Cord Vein ◽

Dependent Mechanism

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Oncostatin M regulates endothelin-1 production in human endothelial cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.2.h662 ◽

1998 ◽

Vol 275 (2) ◽

pp. H662-H667 ◽

Cited By ~ 1

Author(s):

Outi Saijonmaa ◽

Tuulikki Nyman ◽

Päivi Pacek ◽

Frej Fyhrquist

Keyword(s):

Endothelial Cells ◽

Tyrosine Kinase ◽

Kinase Inhibitors ◽

Oncostatin M ◽

Human Umbilical Cord ◽

Kinase Activation ◽

Endothelin 1 ◽

Umbilical Cord Vein ◽

Pkc Activation ◽

Human Umbilical Cord Vein

The effect of the macrophage- and T-lymphocyte-derived cytokine oncostatin M (OSM) on endothelin-1 (ET-1) production in cultured human umbilical cord vein endothelial cells (HUVEC) was studied. OSM (2.5–10 ng/ml) stimulated ET-1 production and the expression of preproendothelin-1 mRNA. The stimulatory effect of OSM was reversed by anti-interleukin (IL)-6 IgG (33 μg/ml). IL-6 (10 ng/ml) was shown to stimulate ET-1 production. The tyrosine kinase inhibitors herbimycin (250–500 ng/ml) and genistein (1–4 μg/ml) suppressed basal ET-1 production and reversed the stimulatory effect of OSM, whereas daidzein (1–8 μg/ml), a less active analog of genistein, had no effect on basal ET-1 production and only partly reversed the stimulatory effect of OSM. The phorbol ester phorbol 12-myristate 13-acetate (PMA) inhibited ET-1 production. Downregulation of protein kinase C (PKC) with PMA (1 μM) preincubation potentiated OSM-induced ET-1 production. In summary, OSM stimulated ET-1 production in cultured HUVEC. The stimulation was probably mediated by IL-6. Furthermore, the present data suggest that tyrosine kinase activation was involved in ET-1 stimulation and that PKC activation leads to suppression of basal and OSM-stimulated ET-1 production.

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