Abstract: SA-PO532
Transgenic LPA Expression Does Not Exacerbate Albuminuria in Diabetic Mice
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Dadi, Amal Omar, Northwestern University, Chicago, Illinois, United States
- Lin, Jennie, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background
Lipoprotein(a) [Lp(a)] is a unique primate-specific and liver-specific lipoprotein consisting of a low-density lipoprotein molecule covalently bonded to an apo(a) protein. Genetically elevated circulating Lp(a) has been identified as an independent causal risk factor for developing coronary heart disease and stroke. We previously showed in a cross-sectional study of patients with type 2 diabetes mellitus that elevated baseline Lp(a) associates with steeper eGFR decline, although no causal link has been firmly established. Here we describe kidney phenotypes resulting from transient adenovirus-induced expression of two different Lp(a) isoforms in diabetic mice.
Methods
In 26-week old DBA/2J mice fed a high-fat diet for 14 weeks, we induced transient liver-specific expression of Lp(a) (truncated or full-length isoform) by adenovirus delivery under a TBG promoter. These sizes were tested due to the proposed role of isoform size in altering Lp(a) plasma concentrations. Plasma and urine samples were serially collected and assayed for metabolic analytes.
Results
Within seven days of adenovirus injection, mice receiving plasmid encoding the truncated LPA isoform or the full-length isoform had robust induction of circulating Lp(a) compared to mice receiving the null plasmid control (1693 +/- 714.3 mg/dL and 207.8 +/- 132.4 mg/dL, respectively, vs. < 6 mg/dL). Baseline mean fasting glucose, blood urea nitrogen, and urinary albumin to creatinine ratios (ACR) were 206.4 mg/dL, 20.3 mg/dL, and 202.9 ug/mg, respectively. Although all mice had increased urinary ACR 4 days post-adenoviral injection, no significant increases in urinary ACR for LPA-expressing mice were seen on days 2, 4, 6, and 7. Consistent with this result, we also did not observe changes in BUN between the LPA-expressing mice and control. No structural differences were observed on histology of kidneys collected 7 days after injection.
Conclusion
Taken together, our results suggest that transient overexpression of Lp(a), does not induce significant worsening of renal function in the short-term. Further studies are needed establish whether a more significant causal effect would be observed with chronic overexpression.
Funding
- Other NIH Support