25-Hydroxycholesterol promotes vascular calcification via activation of endoplasmic reticulum stress.

Vascular calcification is a highly regulated process similar to osteogenesis involving phenotypic change of vascular smooth muscle cells (VSMCs). 25-Hydroxycholesterol (25-HC), one of oxysterols synthesized by the enzyme cholesterol 25-hydroxylase, has been shown to promote bovine calcifying vascular cells (CVC) calcification. However, whether and how 25-HC regulates vascular calcification are not completely understood. In this study, in vitro and ex vivo models of vascular calcification were used to determine whether 25-HC regulates vascular calcification. Alizarin red staining and calcium content assay showed that 25-HC treatment promoted calcification of rat and human VSMCs in a dose-dependent manner. Similarly, ex vivo study further confirmed that 25-HC accelerated calcification of rat aortic rings. In addition, western blot analysis showed that 25-HC significantly up-regulated the expression of endoplasmic reticulum stress (ERS) signaling molecules including ATF4 and CHOP in VSMCs and flow cytometry analysis revealed that 25-HC increased apoptosis of VSMCs. Moreover, knockdown of CHOP by siRNA blocked 25-HC-induced mineral deposition in VSMCs. Collectively, this study for the first time demonstrates that 25-HC promotes vascular calcification via ATF4/CHOP signaling using in vitro and ex vivo models, suggesting that ERS is involved in the regulation of 25-HC-induced vascular calcification.

Dong Q ，Chen Y ，Liu W ，Liu X ，Chen A ，Yang X ，Li Y ，Wang S ，Fu M ，Ou JS ，Lu L ，Yan J ... -  《-》

Endoplasmic Reticulum Stress Mediates Vascular Smooth Muscle Cell Calcification via Increased Release of Grp78 (Glucose-Regulated Protein, 78 kDa)-Loaded Extracellular Vesicles.

Furmanik M ，van Gorp R ，Whitehead M ，Ahmad S ，Bordoloi J ，Kapustin A ，Schurgers LJ ，Shanahan CM ... -  《-》

Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification.

Duan XH ，Chang JR ，Zhang J ，Zhang BH ，Li YL ，Teng X ，Zhu Y ，Du J ，Tang CS ，Qi YF ... -  《-》

Intermedin(1-53) Ameliorates Homocysteine-Promoted Atherosclerotic Calcification by Inhibiting Endoplasmic Reticulum Stress.

Ren JL ，Hou YL ，Ni XQ ，Zhu Q ，Chen Y ，Zhang LS ，Liu X ，Xue CD ，Wu N ，Yu YR ，Tang CS ，Ning ZP ，Chai SB ，Qi YF ... -  《-》

Cortistatin inhibits calcification of vascular smooth muscle cells by depressing osteoblastic differentiation and endoplasmic reticulum stress.

Liu Y ，Lin F ，Fu Y ，Chen W ，Liu W ，Chi J ，Zhang X ，Yin X ... -  《-》