The Role of Endoplasmic Reticulum Stress-Mediated Apoptosis in Vascular Calcification of Chronic Kidney Disease

 Lin Jiang   Lingling Wang   Lingyun Wang   Chen Jiang

Abstract

Vascular calcification refers to the biological regulation process in which hydroxyapatite crystals are actively deposited between the extracellular matrix and arterial intima and media. It increases the risk of cardiovascular complications and death in chronic kidney disease. Chronic kidney disease is affected by the interaction of various physiological or pathological factors, which may lead to endoplasmic reticulum stress and the dysfunction of the endoplasmic reticulum. Endoplasmic reticulum stress plays an important role in apoptosis and is involved in the occurrence and development of vascular calcification. This article reviews the role of endoplasmic reticulum stress-mediated apoptosis in vascular calcification of chronic kidney disease.

Abbreviations :

4-PBA: 4-phenylbutyric acid; AKI: Acute Kidney Injury; ALP: alkaline phosphatase; ASK1: Apoptotic Signal-regulated Kinase 1; ATF4/6: Activated Transcription Factor 4/6; Bad: B-cell leukemia/lymphoma-2-associated death promoter homolog; Bcl-2: B-cell lymphoma 2; Bcl-xl: B-cell lymphoma xl; Bim: Bcl-2 interaction mediator of cell death; cAMP/PKA: cyclic adenylate monophosphate/protein kinase A; CHOP: CCAAT Enhancer Binding Protein (C/EBP) homologous protein; CIHH: Chronic Intermittent Hypobaric Hypoxia; CKD: Chronic Kidney Disease; DN: Diabetic Nephropathy; DR5: Death Receptor 5; EPO: erythropoietin; ERS: Endoplasmic Reticulum Stress; FGF21: Fibroblast Growth Factor 21; GRP78: 78-kDa Glucose-Regulated Protein; Hcy: homocysteine; IMD: intermedin; IRE1: Inositol-Requiring Enzyme 1; JNK: C-Jun N-terminal kinase; MAPK: Mitogen-Actived Protein Kinase; mTORC1: mammalian Target of Rapamycin Complex 1; PERK: Protein ER Kinase (PKR)-like ER kinase; PPARγ: Peroxisome Proliefators-Activated Receptor γ; PUMA: p53 up-regulated modulator of apoptosis; Runx2: runt-related transcription factor 2; TAU: taurine; TNFα: Tumor Necrosis Factor-α; TRAF2: tumor necrosis factor receptor-associated factor 2; UPR: Unfolded Protein Response; VC: Vascular Calcification; VSMC: Vascular Smooth Muscle Cell.