Endoplasmic reticulum stress-mediated apoptosis is activated in vascular calcification.
Apoptosis of vascular smooth muscle cells plays an important role in vascular calcification (VC). However, the potential mechanism remains poorly understood. Previous studies showed that apoptosis mediated by endoplasmic reticulum stress (ERS) participates in several diseases with VC. We prepared two rat models of calcification, vitamin D(3) plus nicotine (VDN) and rapid calcification (RC), to investigate whether ERS-mediated apoptosis is activated in VC. TUNEL staining and cleaved caspase 3 protein levels illustrated enhanced apoptosis in calcification groups. Western blot analysis revealed the ERS hallmarks GRP78 and GRP94 increased by 43.9% and 91.7%, respectively, in the VDN group and GRP78 elevated by 84.0% in the RC group (all P<0.05) as compared with controls. Moreover, two molecules of ERS-induced apoptosis, caspase 12 and C/EBP homologous protein, were up-regulated nearly 3-fold (P<0.05) in the VDN group and 10-fold (P<0.01) in the RC group. Our results indicated that ERS-induced apoptosis may be involved in VC, and amelioration of ERS could be a novel strategy to prevent and treat the related diseases.
Duan
Xiaohui
X
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Zhou
Yebo
Y
Teng
Xu
X
Tang
Chaoshu
C
Qi
Yongfen
Y
D000818:Animals; D017209:Apoptosis; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C018551:glucose-regulated proteins