[parking, VCAM-1 and statins]
just found this, parking only, could also go in the "chronic inflammation" thread. there may be five gazillion similar reports, or this may be lousy science, don't know. not judging, just parking......
Biochem J 2001 Dec 1;360(Pt 2):363-70
Diverse effects of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase on the expression of VCAM-1 and E-selectin in endothelial cells.
Rasmussen LM, Hansen PR, Nabipour MT, Olesen P, Kristiansen MT, Ledet T.
Laboratory for Molecular Pathology, Institute of Pathology, University Hospital of Aarhus, Kommunehospitalet, DK-8000 Aarhus C, Denmark. lmras@dadlnet.dk
The expression of monocyte adhesion molecules, such as VCAM-1 (vascular cell adhesion molecule-1) and E-selectin, on the surface of the endothelium is an important step in the initiation and progression of atherosclerotic lesions. We hypothesized that the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in endothelial cells could influence the expression of VCAM-1 and E-selectin. Using cultured human umbilical vein endothelial cells, we found that mevastatin (0.1-1 microM) significantly reduced the expression of VCAM-1 protein in cells activated by tumour necrosis factor-alpha (TNF-alpha) for 7 h. In contrast, TNF-alpha-induced E-selectin protein expression was augmented after mevastatin treatment. Mevastatin inhibited the mRNA expression of both VCAM-1 and E-selectin in TNF-alpha-stimulated endothelial cells. The activity of the transcription factor nuclear factor-kappa B, which is known to regulate the transcription of VCAM-1 and E-selectin, was significantly reduced after incubation with mevastatin. Analysis of the time-dependent variation in the TNF-alpha-induced expression of E-selectin, and estimation of the rate of surface disappearance of E-selectin together with measurement of the amounts of E-selectin molecules secreted, indicated that mevastatin inhibited the surface removal of E-selectin. This is compatible with the observed increase in E-selectin expression after statin treatment. All observed effects of mevastatin were reversed by mevalonate, the product of the HMG-CoA reductase reaction. In conclusion, inhibition of HMG-CoA reductase in endothelial cells attenuates VCAM-1 expression, but increases E-selectin expression, after cytokine induction. These diverse effects are associated with changes in the transcriptional regulation of the two adhesion molecule genes and modulation of the surface removal of E-selectin. |
