Abstract: FR-PO335
Interleukin-11 Expression Correlates with Hypertensive Kidney Injury in Rat Renovascular Hypertension
Session Information
- Hypertension and CVD: Mechanisms - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Hilgers, Karl F., University of Erlangen, Erlangen, Germany
- Veelken, Roland, University of Erlangen, Erlangen, Germany
- Amann, Kerstin U., University Hospital Erlangen, Erlangen, Germany
- Hartner, Andrea, University Hospital of Erlangen, Erlangen, Germany
Background
Interleukin-11 (IL-11) was recently identified as a crucial determinant of cardiovascular fibrosis (Schafer et al. 2017, Nature 552:110). We examined IL-11 expression in the heart and the kidney exposed to high blood pressure in renovascular hypertensive rats.
Methods
Two-kidney, one-clip renovascular hypertension (2K1C) was induced in rats; controls (CON) were sham operated. IL-11 expression was measured by RT-PCR in the left ventricle and the right kidney (exposed to high blood pressure). The correlation of renal IL-11 expression with several biomarkers of kidney injury was assessed. We further investigated IL-11 expression in 2K1C rats grouped into rats with malignant versus non-malignant hypertension (based on weight loss, and the number of typical fibrinoid necrosis and onion skin lesions per kidney section of the nonclipped kidney).
Results
At 35 days after clipping, mean arterial pressure was 207±4 mmHg in 2K1C versus 113±3 mmHg in CON (p=0.004). IL-11 expression in the right kidney was elevated 19.6±3.3-fold in 2K1C (N=17) compared to CON (N=8, p<0.001). In left ventricular tissue there was only a non-significant trend towards higher IL-11 expression in 2K1C compared to CON (2-fold, p=0.121). IL-11 in the right kidney in 2K1C correlated with the expression of TGFβ (r=0.72, p=0.001), TIMP-1 (r=0.71, p=0.001), collagen 1 (r=0.68, p=0.001), PDGF (r=0.81, p<0.001) as well as with serum creatinine (r=0.52, p=0.036). There were also correlations with parameters of inflammation including MCP-1 expression (r=0.78, p<0.001) and macrophage infiltration (ED-1 staining, r=0.73, p=0.001) but no correlation with mean arterial pressure (p=0.299). Rats with malignant 2K1C (N=8) had the highest levels of IL-11 expression in the kidney (28.3±3.7-fold versus 11.9±4.1-fold in non-malignant 2K1C, N=9; p<0.01 by ANOVA and Bonferroni; CON N=6).
Conclusion
Expression of IL-11 in the kidney of renovascular hypertensive rats is markedly increased and correlates with parameters of fibrosis, inflammation and loss of function.
Funding
- Government Support - Non-U.S.