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GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu
- Source :
- Jerotic, D, Suvakov, S, Matic, M, Alqudah, A, Grieve, D J, Pljesa-Ercegovac, M, Savic-Radojevic, A, Damjanovic, T, Dimkovic, N, McClements, L & Simic, T 2021, ' GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu ', Oxidative Medicine and Cellular Longevity, vol. 2021, 6678924 . https://doi.org/10.1155/2021/6678924, Oxidative Medicine and Cellular Longevity, Vol 2021 (2021), Oxidative Medicine and Cellular Longevity
- Publication Year :
- 2021
-
Abstract
- Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD.
- Subjects :
- Aging
Proteome
medicine.medical_treatment
030232 urology & nephrology
030204 cardiovascular system & hematology
medicine.disease_cause
Biochemistry
0302 clinical medicine
Malondialdehyde
11 Medical and Health Sciences
Glutathione Transferase
Chemistry
Cell adhesion molecule
General Medicine
Intercellular Adhesion Molecule-1
medicine.anatomical_structure
Cytokine
Cytokines
medicine.symptom
Research Article
medicine.medical_specialty
Article Subject
Angiogenin
Vascular Cell Adhesion Molecule-1
Inflammation
Proinflammatory cytokine
03 medical and health sciences
Downregulation and upregulation
SDG 3 - Good Health and Well-being
Internal medicine
Human Umbilical Vein Endothelial Cells
medicine
Humans
Uremia
Glutathione Peroxidase
QH573-671
Superoxide Dismutase
Monocyte
Cell Biology
Oxidative Stress
Ageing
Endocrinology
Kidney Failure, Chronic
Reactive Oxygen Species
Cytology
Biomarkers
Gene Deletion
Oxidative stress
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Jerotic, D, Suvakov, S, Matic, M, Alqudah, A, Grieve, D J, Pljesa-Ercegovac, M, Savic-Radojevic, A, Damjanovic, T, Dimkovic, N, McClements, L & Simic, T 2021, ' GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu ', Oxidative Medicine and Cellular Longevity, vol. 2021, 6678924 . https://doi.org/10.1155/2021/6678924, Oxidative Medicine and Cellular Longevity, Vol 2021 (2021), Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....b726c18cdd8cc120d0a57e19d57b2738