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Published on: August 12, 2025
Uremic serum induces proatherogenic changes in human endothelial cells
Gianluca Fasoli1, Ciro Esposito, Flavia Cornacchia
1Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Pavia-Italy.
Insights
Uremic serum promotes atherosclerosis by damaging endothelial cells, increasing mononuclear cell adhesion and collagen production. This study reveals a key mechanism in cardiovascular complications for uremic patients.
Area of Science:
- Vascular Biology
- Nephrology
- Cardiovascular Research
Background:
- Cardiovascular complications are the primary cause of mortality in patients with uremia.
- Uremic angiopathy is characterized by accelerated atherosclerosis, but the underlying mechanisms of vessel wall injury remain unclear.
- This study investigates the hypothesis that uremic serum induces a proatherogenic state in endothelial cells.
Purpose of the Study:
- To determine the effects of uremic serum on human endothelial cells (HECs).
- To evaluate endothelial cell proliferation, apoptosis, nitric oxide (NO) production, and mononuclear cell adhesion.
- To assess the impact of uremic serum on collagen production and the expression of specific mRNA.
Main Methods:
- Human endothelial cells (HECs) were incubated with uremic serum.
- Cell proliferation, apoptosis, and collagen production were measured using cell counting and ELISA.
- Nitric oxide (NO) levels were assessed by measuring nitrite/nitrate concentrations.
- mRNA levels of (alfa2)IV collagen, TIMP-1, and TGF-beta were quantified using RT-PCR.
- Experiments included preincubation with anti-receptor for advanced glycation end product (anti-RAGE) antibodies.
Main Results:
- Uremic serum did not affect HEC proliferation but induced apoptosis after 72 hours.
- Mononuclear cell adhesion to HEC monolayers was significantly increased by uremic serum.
- Uremic serum elevated mRNA levels of (alfa2)IV collagen, TIMP-1, and TGF-beta.
- No increase in nitric oxide (NO) concentration was observed in uremic serum-treated cells.
- TGF-beta expression was not altered by L-NAME or anti-RAGE antibodies.
Conclusions:
- Uremic serum induces a proatherogenic state in human endothelial cells (HECs).
- This effect may contribute to the accelerated atherosclerosis observed in uremic patients.
- The proatherogenic effects of uremic serum do not appear to be mediated by nitric oxide (NO) or advanced glycation end products (AGEs).
Background:
Cardiovascular complications are the main cause of death in uremic patients. Uremic angiopathy has been regarded as an accelerated form of atherosclerosis. However the mechanism leading to vessel wall injury is still unknown. We hypothesized that uremic serum affects endothelium inducing a proatherogenic state.
Methods:
We studied the effects of uremic serum on human endothelial cells (HECs). Cell proliferation and adhesion of mononuclear cells to HEC monolayers were evaluated by cell counting, apoptosis and collagen production by ELISA, and nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant. (alfa2)IV collagen, tissue inhibitor of metalloproteases-1 (TIMP-1) and transforming growth factor-beta (TGF-beta) mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR). In some experiments cells were preincubated with anti-receptor for advanced glycation end product (anti-RAGE) blocking antibodies.
Results:
Uremic serum did not modify HEC proliferation but induced apoptosis after 72 hours of incubation. Adhesion of mononuclear cells to HEC monolayers was significantly increased by uremic serum. In addition, uremic serum increased (alfa2)IV collagen, TIMP-1 and TGF-beta mRNA levels. There was no increase in nitric oxide concentration in ure-mic serum-treated endothelial cells, and the expression of TGF-beta was neither modified by L-NAME nor by anti-RAGE antibodies.
Conclusions:
Our results indicate that uremic serum affects HEC inducing a proatherogenic state that may be responsible for the accelerated atherosclerosis of uremic patients. Apparently uremic serum effect is not mediated by NO or by AGEs.
