title: Valsartan protects HK-2 cells from contrast media-induced apoptosis by inhibiting endoplasmic reticulum stress.
abstract: Contrast-induced acute kidney injury (CI-AKI) is associated with increasing in-hospital and long-term adverse clinical outcomes in high-risk patients undergoing percutaneous coronary intervention (PCI). Contrast media (CM)-induced renal tubular cell apoptosis is reported to participate in this process by activating endoplasmic reticulum (ER) stress. An angiotensin II type 1 receptor (AT1R) antagonist can alleviate ER stress-induced renal apoptosis in streptozotocin (STZ)-induced diabetic mice and can reduce CM-induced renal apoptosis by reducing oxidative stress and reversing the enhancement of bax mRNA and the reduction of bcl-2 mRNA, but the effect of the AT1R blocker on ER stress in the pathogenesis of CI-AKI is still unknown. In this study, we explored the effect of valsartan on meglumine diatrizoate-induced human renal tubular cell apoptosis by measuring changes in ER stress-related biomarkers. The results showed that meglumine diatrizoate caused significant cell apoptosis by up-regulating the expression of ER stress markers, including glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein-homologous protein (CHOP) and caspase 12, in a time- and dose-dependent manner, which could be alleviated by preincubation with valsartan. In conclusion, valsartan had a potential nephroprotective effect on meglumine diatrizoate-induced renal cell apoptosis by inhibiting ER stress.
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Ping-An
authors.initials: PA
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Experimental Center, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Hong-Ya
authors.initials: HY
authors.lastname: Han
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Ji
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003287:Contrast Media / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D003287:Contrast Media; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D020011:Protective Agents; D000068756:Valsartan
keywords: apoptosis; contrast media; endoplasmic reticulum stress; valsartan