Intermedin1–53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate/protein kinase A pathway. (October 2013)

• Record Type: Journal Article
• Authors: Chang, Jin-Rui; Duan, Xiao-Hui; Zhang, Bao-Hong; Teng, Xu; Zhou, Ye-Bo; Liu, Yue; Yu, Yan-Rong; Zhu, Yi; Tang, Chao-Shu; Qi, Yong-Fen
• Is Part Of: Experimental biology and medicine. Volume 238:Number 10(2013)
• Page Start: 1136
• Page End: 1146
• Publication Date: 2013-10
• Subjects: intermedin1–53 -- vascular calcification -- endoplasmic reticulum stress -- apoptosis; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370213502619
• Languages: English
• ISSNs: 1535-3702

Abstract

We previously reported that endoplasmic reticulum (ER) stress-mediated apoptosis participated in vascular calcification. Importantly, a novel paracrine/autocrine peptide intermedin1–53 (IMD1–53 ) in the vasculature inhibited vascular calcification in rats. But the mechanisms needed to be fully elucidated. Vascular smooth muscle cells (VSMCs) calcification was induced by CaCl2 and β-glycerophosphate. Tunicamycin (Tm) or dithiothreitol (DTT) was used to induce ER stress. We found that IMD1–53 (10 −7 mol/L) treatment significantly alleviated the protein expression of ER stress hallmarks activating transcription factor 4 (ATF4), ATF6, glucose-regulated protein 78 (GRP78) and GRP94 induced by Tm or DTT. ER stress occurred in early and late calcification of VSMCs but was inhibited by IMD1–53 . These inhibitory effects of IMD1–53 were abolished by treatment with the protein kinase A (PKA) inhibitor H89. Pretreatment with IMD1–53 decreased the number of apoptotic VSMCs and downregulated protein expression of cleaved caspase 12 and C/EBP homologous protein (CHOP) in calcified VSMCs. Concurrently, IMD1–53 restored the loss of VSMC lineage markers and ameliorated calcium deposition and alkaline phosphatase activity in calcified VSMCs as well. The observation was further verified by Alizarin Red S staining, which showed that IMD1–53 reduced positive red nodules among calcified VSMCs. In conclusion, IMD1–53 attenuated VSMC calcification by inhibiting ER stress through cAMP/PKA signalling.