Intermedin1–53 attenuated endoplasmic reticulum stress (ERS) induced by homocysteine (Hcy) in vivo and in vitro. Western blot analysis of protein levels (a, b) of ERS hallmarkers such as glucose-regulated protein 78 (GRP78) and GRP94, activating transcription factor 6 (ATF6), phosphorylated inositol-requiring enzyme 1α (p-IRE1α), spliced-Xbox-binding protein-1 (s-XBP-1), phosphorylated protein kinase receptor-like ER kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) and ATF4 in the myocardium of ApoE-/- mice in vivo. Western blot analysis of protein levels (c, d) of ERS hallmarkers such as ATF6, ATF4, GRP94, GRP78, p-eIF2α, p-PERK, p-IRE1α, and s-XBP-1 in rat cardiac fibroblasts in vitro. Glyceraldehyde-3-phosphate dehydrogenase was a loading control. Data are mean ± SD, n = 3 in each group; *P < 0.05 and **P < 0.01 versus Con. #P < 0.05 and ##P < 0.01 versus Hcy.