期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 451, 期 3, 页码 436-441出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.08.007
关键词
Vascular smooth muscle cell; Ectopic calcification; Hyperphosphatemia; Microtubule
资金
- Korea Healthcare Technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea [A120596]
- National Research Foundation of Korea, Korea [2013R1A1A2A10006677, 2013R1A1A2057481]
- National Research Foundation of Korea [2013R1A1A2057481, 2013R1A1A2A10006677] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Vascular calcification is a strong predictor of cardiovascular morbidity and mortality, especially in individuals with chronic kidney disease or diabetes. The mechanism of vascular calcification has remained unclear, however, and no effective therapy is currently available. Our study was aimed at identifying the role of dynamic remodeling of microtubule cytoskeletons in hyperphosphatemia-induced vascular calcification. Exposure of primary cultures of mouse vascular smooth muscle cells (VSMCs) to inorganic phosphate (Pi) elicited ectopic calcification that was associated with changes in tubulin dynamics, induction of osteogenic signaling, and increased release of matrix vesicles. A microtubule depolymerizing agent enhanced Pi-dependent calcification, whereas microtubule stabilization by paclitaxel suppressed calcification both in VSMC cultures and in an ex vivo culture system for the mouse aorta. The inhibition of Pi-stimulated calcification by paclitaxel was associated with down-regulation of osteogenic signal and attenuation of matrix vesicle release. Our results indicate that microtubule plays a central role in vascular calcification, and that microtubule stabilization represents a potential new approach to the treatment of this condition. (C) 2014 Elsevier Inc. All rights reserved.
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