Warfarin accelerated vascular calcification and worsened cardiac dysfunction in remnant kidney mice |
| |
Authors: | Ming-Tsun Tsai Ying-Ying Chen Wei-Jeng Chang Szu-Yuan Li |
| |
Affiliation: | 1. Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital Taoyuan Branch, Taoyuan, Taiwan, ROC;2. National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC;3. Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC;4. National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan, ROC |
| |
Abstract: | BackgroundVascular calcification is highly prevalent in end-stage renal disease (ESRD) and is a significant risk factor for future cardiovascular events and death. Warfarin use results in dysfunction of matrix Gla protein, an inhibitor of vascular calcification. However, the effect of warfarin on vascular calcification in patients with ESRD is still not well characterized. Thus we investigated whether arterial calcification can be accelerated by warfarin treatment both in vitro and in vivo using a mouse remnant kidney model.MethodsHuman aortic smooth muscle cells (HASMC) were cultured in medium supplemented with warfarin and phosphate to investigate the potential role of this drug in osteoblast transdifferentiation. For in vivo study, adult male C57BL/6 mice underwent 5/6 nephrectomy were treated with active vitamin D3 plus warfarin to determine the extent of vascular calcification and parameters of cardiovascular function.ResultsWe found that the expressions of Runx2 and osteocalcin in HASMC were markedly enhanced in the culture medium containing warfarin and high phosphate concentration. Warfarin induced calcification of cultured HASMC in the presence of high phosphate levels, and this effect is inhibited by vitamin K2. Severe aortic calcification and reduced left ventricular ejection fractions were also noted in 5/6 nephrectomy mice treated with warfarin and active vitamin D3.ConclusionWarfarin treatment contributes to the accelerated vascular calcification in animal models of advanced chronic kidney disease. Clinicians should therefore be aware of the profound risk of warfarin use on vascular calcification and cardiac dysfunction in patients with ESRD and atrial fibrillation. |
| |
Keywords: | Left ventricular dysfunction Uremia Vascular calcification Warfarin |
本文献已被 ScienceDirect 等数据库收录! |
|