Abstract: FR-PO208

Induction of Unique Scavenger Receptor Dysregulation Pattern in Advanced CKD

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Miyawaki, Nobuyuki (Bill), NYU Winthrop Hospital, Mineola, New York, United States
  • Siegart, Nicolle Marie, NYU Winthrop Hospital, Mineola, New York, United States
  • Daccueil, Farah, NYU Winthrop Hospital, Mineola, New York, United States
  • De leon, Joshua, NYU Winthrop Hospital, Mineola, New York, United States
  • Mattana, Joseph, NYU Winthrop Hospital, Mineola, New York, United States
  • Kasselman, Lora, NYU Winthrop Hospital, Mineola, New York, United States
  • Reiss, Allison B., NYU Winthrop Hospital, Mineola, New York, United States
Background

In chronic kidney disease (CKD), scavenger receptors (SR) are the main cholesterol entry paths into macrophages, bypassing the regulated LDL receptors, to accelerate foam cell production in synergy with defective cholesterol efflux. Yet alteration patterns of SR in CKD remain poorly defined.

Methods

Following THP-1 human macrophage (106/ml) incubation for 24h with 10% plasma from 10 CKD Stage 4+5 patients (without diabetes, rheumatological illnesses or active infections) or plasma from 10 healthy control subjects, mRNA was isolated and reverse transcribed. The resulting cDNA was subjected to quantitative real-time PCR using specific primers for major cholesterol scavenger receptors CD36, LOX-1, SR-A1 as well as efflux proteins, ATP binding cassette transporter (ABC)A1 and G1.

Results

Exposure to CKD plasma decreased the expression of scavenger receptor CD36 with a 32% reduction (Fold change with CKD plasma exposure: 0.68, 95% CI [0.54, 0.87], p<0.01). SR-A1 expression with CKD plasma exposure was unaffected with a fold change of 0.80, 95% CI [0.52, 1.24], p<0.01). LOX-1 expression was not reduced; rather a very strong trend to LOX-1 enhancement with 1.54-fold increase with CKD plasma exposure (95% CI [1.01, 2.35], p=0.053). Downregulation of ABCA1 and ABCG1 were demonstrated, respectively, by 33% (0.67, 95% CI [0.04, 0.92], p=0.01) and by 30% (0.70, 95% CI [0.50, 0.98], p=0.03).

Conclusion

Prior studies of CKD populations have evaluated isolated SR and often without exclusion of other known inflammatory conditions which impact SR dysregulation patterns. Our demonstration of decreased CD36, unaffected SR-A1 and a very strong suggestion of increased LOX-1 in CKD differs from those previously described in rheumatoid arthritis or lupus and may provide future avenues for viable therapeutic targets. Additional studies on LOX-1 as well as impact of its inhibition may be helpful in further elucidation of SR mediated uptake mechanisms in CKD. Reduced ABC gene expression likely lowers defense against lipid overload and may be a target for therapeutic intervention.

Funding

  • Private Foundation Support