Abstract: TH-PO073

Lipoproteins Modulate Podocyte Damage and Proteinuria

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • Tsuchida, Yohei, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Fogo, Agnes B., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Matsusaka, Taiji, Tokai University School of Medicine, Isehara, KANAGAWA, Japan
  • Yang, Haichun, Vanderbilt University, Nashville, Tennessee, United States
  • Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Although high density lipoprotein (HDL) and its main protein, apolipoprotein AI (apoAI) have established benefits in various cell types, their effects on renal cells remain unclear. We investigated the consequences of exposing normal and damaged podocytes to normal apoAI/HDL (HDLCont), apoAI mimetic (L-4F), and HDL from patients with established CKD known to have dysfunctional (HDLCKD).

Methods

In vitro, primary mouse podocytes were injured by puromycin (PAN) and cellular viability, proliferation, migration and cellular production of reactive oxygen species (ROS) assessed. In vivo, transgenic mice expressing human CD25 in podocytes that can be selectively injured by injection of immunotoxin were used as the proteinuric model. At injury, half the mice recieved L-4F x 2 wks. Urinary albumin-creatinine ratio (ACR) was measured and expression of podocyte markers, synaptopodin and WT1 assessed.

Results

PAN reduced podocyte viability, proliferation, migration and increased ROS production in vitro. Each of these perturbations was significantly lessened by apoAI and HDLCont but not HDLCKD (Table). Critically, while maximum proteinuria was similar in treated and untreated mice, L-4F significantly accelerated ACR reduction and preserved podocyte expression of synaptopodin and WT1-positive cell density.

Conclusion

The results indicate that normal apoAI and HDL, but not dysfunctional HDLCKD protect against podocyte damage. ApoAI mimetic provides in vivo benefits to podocytes culminating in reduced albuminuria. We suggest supplemental apoAI may be a novel candidate to lessen podocyte damage and proteinuria.

Funding

  • Other NIH Support