|
|||||
|
|
T0901317, an LXR agonist, augments PKA-induced vascular cell calcification |
|
| Authors: | Jeffrey J. Hsu Michael S. Huang Andrew P. Sage Peter Tontonoz Linda L. Demer Yin Tintut |
| Affiliation: | a Department of Medicine, David Geffen School of Medicine at UCLA, CHS A2-237, 10833 Le Conte Avenue, Los Angeles, CA 90095-1679, USA b Department of Physiology, University of California at Los Angeles, CA 90095, USA c Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California at Los Angeles, CA 90095, USA |
| Abstract: | We examined the effect of liver X receptor (LXR) agonists on vascular calcification, prevalent in atherosclerotic lesions. T0901317, an LXR agonist, augmented protein kinase A (PKA)-induced mineralization and alkaline phosphatase (ALP) activity in aortic smooth muscle cells isolated from wild-type, but not from Lxrβ−/−mice. A six-hour T0901317 treatment augmented the PKA-induced expression of the phosphate transporter Pit-1, a positive regulator of mineralization, suggesting a direct role. A ten-day T0901317 treatment attenuated PKA-induced expression of mineralization inhibitors, osteopontin and ectonucleotide pyrophosphatase/phosphodiesterase-1, suggesting an indirect role. The effects of T0901317 were attenuated by inhibition of ALP, Pit-1 and Rho-associated kinase, but not by inhibition of PKA. These results suggest that T0901317-augmented mineralization occurs downstream of PKA, involving both direct and indirect LXR-mediated pathways. |
| Keywords: | T0901317 Liver X receptor Calcification Smooth muscle cell |
| 本文献已被 ScienceDirect 等数据库收录！ | |