Abstract: FR-PO202

Nephrotic Syndrome Modulates Flow and Composition of Mesenteric Lymph

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Banan, Babak, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Albaugh, Vance L, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Tsuchida, Yohei, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Yancey, Patricia G., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wiese, Carrie B., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Vickers, Kasey C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Although hyperlipidemia and altered lipid/lipoprotein metabolism that characterize nephrotic syndrome (NS) are usually ascribed to functional changes in the liver, little is understood about how NS impacts another relevant organ system, i.e., gut. Small intestine functions not only to reabsorb dietary lipids but also contributes to lipoprotein synthesis, particularly apolipoprotein AI, the main protein in high density lipoprotein (HDL) that provides beneficial effects to many different tissues. All reabsorbed lipids and synthesized lipoproteins are taken-up and transported through the lymphatics. Since integral to NS is development of edema that reflects lymphatic inadequacy, we examined the lymphatic network in a model of NS.

Methods

NS was induced by puromycin aminonucleoside (PAN) in 12 Sprague Dawley rats, while 12 non-injected rats served as control (C). Eight days later, plasma, urine, mesenteric lymph, kidney and ileum were collected for further analysis.

Results

Along with massive proteinuria, PAN significantly increased plasma cholesterol and triglyceride that was accompanied by increased renal lymphatic vessel density (assessed by staining for podoplanin). Proteinuric injury caused a 6-fold increase in mesenteric lymph flow (PAN:10.7±1.3ml vs C:1.5±0.3 x 3h, p<0.001). Despite apparent dilution, the mass of cholesterol and triglycerides transported by mesenteric lymph over time was 3- and 5-fold higher in PAN than C (both p<0.05). PAN dramatically increased lymphatic transport of apoAI (PAN:108.3±13.0μg vs C:13.7±2.6 x 3 hours p<0.001). While plasma cytokines (IL-6, IL-10, IL-1, IL-17a) were not different, PAN significantly increased lymphatic concentration of IL-6 (>200%, p<0.05), IL-10 (>150%, p<0.05) and IL-17a (>200%, p<0.05). In addition, PAN raised the number of Th17 cells (>50%, p<0.05) and increased the level of VEGFA (>100%, p<0.05) compared to C.

Conclusion

Proteinuric kidney injury expands the renal lymphatic network and enhances mesenteric lymph flow which carries more fluid, lipids, lipoproteins, inflammatory cytokines and growth factors. These data suggest a potentially critical role for the intestinal lymphatic network in edema, inflammation and cardiovascular complications of NS and present a new target to lessen these complications.

Funding

  • Other NIH Support