Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20 ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling.
Kenichi Serizawa, Kenji Yogo, Yoshihito Tashiro, Satoshi Takeda, Ryohei Kawasaki, Ken Aizawa and Koichi Endo
De-Fu Ma, Katsuko Sudo, Hideo Tezuka, Tetsuo Kondo, Tadao Nakazawa, Dong-Feng Niu, Tomonori Kawasaki, Kunio Mochizuki, Tetsu Yamane and Ryohei Katoh
We report the first demonstration of the embryonal patch patterns of endocrine organs and the polyclonality of hormone-producing cell populations using chimeric mice produced by aggregation of C57BL/6-Tg(CAG-EGFP)C14-Y01-FM131Osb transgenic mice and BALB/C mice. Confocal laser scanning microscopy (CLSM) analysis for enhanced green fluorescent protein (EGFP) and immunohistochemistry with anti-EGFP antibody revealed that all endocrine organs of chimeric mice had a mosaic appearance of EGFP-positive patches and EGFP-negative patches. The patches composed of EGFP-positive cells were distinctive in their size and shape. The pituitary patches were large and irregular, representing a geographical pattern. In contrast, parathyroid, pancreatic islet, and adrenal medulla patches were small and demarcated, representing an island-like pattern. Thyroid follicles and adrenal cortex cords showed a mixture of monophenotypia and polyphenotypia, indicating polyclonal embryonic origin. Furthermore, we studied the tissue clonality of hormone-producing cell populations in the pituitary, thyroid, and pancreatic islets using a combination method of CLSM for EGFP and immunohistochemistry for hormones. All the pituitary cell populations of GH, prolactin, TSH, FSH, LH, and ACTH, the calcitonin-producing cell population in the thyroid, and the insulin- and glucagon-producing cell populations in pancreatic islets had mosaic patterns in EGFP expression in the chimeric mice, suggesting polyclonal embryonic origin. In conclusion, the different patch patterns of the endocrine organs could contribute to the understanding of embryonic development and organization of endocrine organs. Furthermore, we clearly demonstrate that all hormone-producing cell populations are of polyclonal embryonic origin, derived from more than two progenitor cells.