Abstract: TH-PO401

HDL from CKD Rabbits and Hemodialysis Patients Exhibit Impaired Anti-Aggregative Activity on Human Platelets through CD36 Pathway

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Florens, Nans, Hospices Civils de Lyon, Lyon, France
  • Calzada, Catherine, CarMeN, INSERM, U1060, INSA Lyon, Villeurbanne, France
  • Yi, Dan, CarMeN, INSERM, U1060, INSA Lyon, Villeurbanne, France
  • Lemoine, Sandrine, Hospices Civils de Lyon, Lyon, France
  • Juillard, Laurent, Hospices Civils de Lyon, Lyon, France
  • Soulage, Christophe O., CarMeN, INSERM, U1060, INSA Lyon, Villeurbanne, France
Background

Recent studies have shown altered biological properties of HDL in chronic kidney disease (CKD). As cardiovascular mortality remains the major cause of death in CKD and as oxidative stress is raised in CKD, we aimed to explore the specific role of oxidative modifications of HDL in CKD and their impact on anti-aggregant phenotype of HDL.

Methods

Rabbits were surgically 5/6-nephrectomized. Blood from healthy volunters (control) were sampled during their live-donor evaluation visit. Hemodialysis (HD) patients were sampled before the HD session. HDL were separated from plasma by potassium bromide stepwise density gradient ultracentrifugation. In rabbits, Malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and 4-hydroxy-2-hexenal (HHE) protein adducts levels were assayed. Platelet aggregation was measured after 5 min of incubation with HDL from each group in an aggregometer with or without anti-CD36 blocking antibody (Ab-CD36). HDL from control rabbits were modified by an incubation overnight at 37°C with 100mM of HNE.

Results

8 CKD were compared with 9 Sham operated rabbits. CKD rabbits exhibited a higher creatinine level than the control group (93 ± 12 vs 214 ± 25 µM, p<0.001). MDA contents were significantly higher in the HDL from CKD group (0.89 ± 0.18 vs 2.64 ± 0.67 nmol/mg, p<0.05). HNE-adducts were also increased in HDL from CKD animals while HHE-adducts levels were not different. Percentage of platelet aggregation (PA) compared to collagen alone was 65% when were incubated with HDL from CKD group while it was 30% with HDL from the control group (p<0.05) evidencing a blunted anti-aggregative effect. PA in presence of HNE-modified HDL was 85% (p<0.05 compared to Control group). Incubation with Ab-CD36 decreased the PA with CKD and HNE-modified HDL to 27 and 23%, respectively (p<0.05).
5 control patients were compared with 6 HD patients. Percentage of PA compared to collagen alone with HDL from HD patients was higher than in the control group (63 vs 24%, p<0.01).

Conclusion

CKD is associated with oxidative modifications of HDL among which HNE-adducts. HDL from CKD rabbits and HD patients exhibited an impaired ability to inhibit platelet aggregation suggesting that altered HDL properties could contribute to the increased cardiovascular risk in this population.