KLF2 Suppresses Vascular Calcification through Inhibition of Endothelial BMP/Smad1/5 Pathway
Refereed conference paper presented and published in conference proceedings


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摘要Vascular calcification is a common vascular complication of atherosclerosis, diabetes, and fibrotic renal diseases, and is associated with an increased risk of cardiovascular mortality. Endothelial cells are constantly exposed to mechanical forces generated by blood flow. Different flow patterns induce distinct cellular responses. Disturbed flow (DF) induces vascular inflammation and promotes atherogenesis, while laminar shear stress (LSS) produces anti-inflammatory and athero-protective effects. We found that vascular calcification preferentially develops at arterial branches and curvatures where the main flow pattern is DF in ApoE−/− mice fed with atherogenic diet for 26 weeks. Interestingly, we observed that Kruppel-like factor 2 (KLF2), a shear stress-responsive transcription factor, decreases in the calcified human aortic valves, suggesting an inhibitory role of KLF2 in vascular calcification. Our in vitro studies showed that KLF2 negatively regulate BMP/Smad1/5 pathway that plays a critical role in the pathogenesis of vascular calcification. Besides, we found that DF activates BMP/Smad signaling and KLF2 overexpression reverses the DF-induced activation of BMP/Smad signaling. Our present study suggests that targeting the KLF2-BMP/Smad signaling cascade may hold promise as a novel drug target against vascular calcification.
(The study was supported by Hong Kong RGC-CRF C4024-16W and RGC-GRF 14109618).
著者Juan HUANG, Jiangyun LUO, Yu HUANG
會議名稱Vascular Discovery: From Genes to Medicine
會議開始日14.05.2019
會議完結日16.05.2019
會議地點Boston, USA
會議國家/地區美國
會議論文集題名Arteriosclerosis, Thrombosis, and Vascular Biology
出版年份2019
月份5
卷號39
期次Suppl 1
文章號碼A719
國際標準期刊號1079-5642
電子國際標準期刊號1524-4636
語言美式英語

上次更新時間 2020-13-09 於 01:55