| Title | Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification |
| Authors | Duan, Xiao-Hui Chang, Jin-Rui Zhang, Jing Zhang, Bao-Hong Li, Yu-Lin Teng, Xu Zhu, Yi Du, Jie Tang, Chao-Shu Qi, Yong-Fen |
| Affiliation | Capital Med Univ, Key Lab Remodeling Related Cardiovasc Dis, Minist Educ, Beijing An Zhen Hosp, Beijing 100029, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China. Beijing Normal Univ, Sch PE & Sports Sci, Beijing 100875, Peoples R China. Hosp Tsinghua Univ, Beijing 100084, Peoples R China. |
| Keywords | Activating transcription factor 4 Endoplasmic reticulum stress Apoptosis Vascular calcification UNFOLDED PROTEIN RESPONSE SMOOTH-MUSCLE-CELLS CHEMICAL CHAPERONES TAURINE PREVENTS MODEL MECHANISMS EXPRESSION |
| Issue Date | 2013 |
| Publisher | apoptosis |
| Citation | APOPTOSIS.2013,18,(9),1132-1144. |
| Abstract | Our previous work reported that endoplasmic reticulum stress (ERS)-mediated apoptosis was activated during vascular calcification (VC). Activating transcription factor 4 (ATF4) is a critical transcription factor in osteoblastogenesis and ERS-induced apoptosis. However, whether ATF4 is involved in ERS-mediated apoptosis contributing to VC remains unclear. In the present study, in vivo VC was induced in rats by administering vitamin D-3 plus nicotine. Vascular smooth muscle cell (VSMC) calcification in vitro was induced by incubation in calcifying media containing beta-glycerophosphate and CaCl2. ERS inhibitors taurine or 4-phenylbutyric acid attenuated ERS and VSMC apoptosis in calcified rat arteries, reduced calcification and retarded the VSMC contractile phenotype transforming into an osteoblast-like phenotype in vivo. Inhibition of ERS retarded the VSMC phenotypic transition into an osteoblast-like cell phenotype and reduced VSMC calcification and apoptosis in vitro. Interestingly, ATF4 was activated in calcified aortas and calcified VSMCs in vitro. ATF4 knockdown attenuated ERS-induced apoptosis in calcified VSMCs. ATF4 deficiency blocked VSMC calcification and negatively regulated the osteoblast phenotypic transition of VSMCs in vitro. Our results demonstrate that ATF4 was involved at least in part in the process of ERS-mediated apoptosis contributing to VC. |
| URI | http://hdl.handle.net/20.500.11897/220971 |
| ISSN | 1360-8185 |
| DOI | 10.1007/s10495-013-0861-3 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
