Abstract: SA-PO296

The Kidneys and the Lungs in the Rat Show Different Vascular and Fibrotic Changes in an Acute Model of Fat Embolism in the Presence or Absence of the Renin Inhibitor Aliskiren

Session Information

Category: Cell Biology

  • 204 Extracellular Matrix Biology, Fibrosis, Cell Adhesion

Authors

  • Elsherbiny, Hisham, University of Missouri at Kansas CIty, Kansas City, Missouri, United States
  • Khalafi, Farnaz, University of Missouri at Kansas City, Kansas City, Missouri, United States
  • Vaidyanathan, Vaishnavi Lakshmi, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • Poisner, Alan, Univ of Kansas Medical Center, Overland Park, Kansas, United States
  • Arif, Dauod, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • Siddiqi, Ahsan, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • Molteni, Agostino, University of Missouri at Kansas City, Kansas City, Missouri, United States
Background

In a rat model of fat embolism (FE) induced by injection of triolein (T), a severe inflammatory reaction leads to vasculitis and pulmonary fibrosis that was mitigated by drugs interfering with the renin angiotensin system (RAS): a renin inhibitor aliskiren (ALI).
We extended the study to the kidneys by evaluating the renal arterial response to T treatment in this FE model and the effect of ALI .

Methods

22 Sprague Dawley rats received T (0.2 ml IV, n=18) or saline (n=4). The T-treated rats were divided into three groups of 6 rats each and injected IP one hour later, with saline, ALI 50mg/kg or ALI 100mg/kg. Four controls received saline. Rats were killed 48 hours later; the organs fixed and stained with H&E, trichrome and smooth muscle actin (SMA). The vascular evaluation included lumen patency (LP) and media adventitia ratio (MAR), a marker of edema. Photos at 400 X and 100 X were taken on each slide by two pathologists unaware of the slide identity.
Alpha SMA and trichrome-stained slides were digitally analyzed by image J software (NIH) to quantify the amount of myofibroblasts and collagen present in each slide.

Results

Rats injected with T + saline showed the expected severe pulmonary vascular inflammation markedly reduced by both ALI doses but no significant inflammatory response was observed in the kidneys. T + ALI 50 showed a significant (p<0.01) increase in pulmonary lumen patency vs the T + saline group which revealed only a trend in reduction vs the controls. No differences in lumen patency were seen for renal arteries. The pulmonary MAR measurements were similar in the four groups whereas there was a significant effect in the kidneys (p<0.0007) with a slightly larger ratio for the T +saline and T + ALI groups. Image J determination revealed other organ differences with ALI reducing alpha SMA and trichrome in lungs but not in kidneys. An opposite trend was seen in the MAR where T +ALI showed a return toward control values vs the T + saline induced increase while no difference among treatments were observed in lungs.

Conclusion

MAR differences suggest that FE has some renal vascular effects in this acute model mediated by the RAS, albeit different from that in the lungs.

Funding

  • Private Foundation Support