Abstract: PO1833
RNA Sequencing Reveals Induction of Specific Renal Inflammatory Pathways in a Rat Model of Malignant Hypertension
Session Information
- Hypertension and CVD: Mechanisms
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Hartner, Andrea, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Menendez-Castro, Carlos, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Cordasic, Nada, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Ekici, Arif, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Daniel, Christoph, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
- Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
Background
In malignant hypertension (MH), far more severe kidney injury occurs than in the “benign” form of the disease. The pathogenesis of this peculiar renal injury of malignant hypertension remains incompletely understood. Using a rat model in which some but not all animals develop MH, we performed an unbiased analysis of gene expression by RNA-sequencing to identify transcriptional changes in the kidney specific for malignant hypertension.
Methods
Renovascular hypertension in rats was induced by placing a 0.2 mm clip on the left renal artery (2K1C). Five weeks later, all 2K1C rats had developed hypertension. Rats were then sacrificed, and renal cortical RNA was extracted from the right kidney exposed to high blood pressure. To distinguish MH from non-malignant hypertension (NMH), we considered two factors: weight loss and typical renovascular lesions.Differential gene expression was assessed in three groups: MH, NMH and normotensive, sham operated controls (N=5 per group for RNA sequencing, N between 8 and 14 for other analyses).
Results
Mean blood pressure measured intraarterially was elevated to a similar degree in MH (207±10 mmHg) and NMH (201±4 mmHg) compared to controls (113±3 mmHg, p<0.05). 886 genes were exclusively regulated in MH only. Principal component analysis revealed a separated clustering of the three groups. The data pointed to an upregulation of many inflammatory mechanisms in MH including pathways which previously attracted little attention in this setting: Transcripts from all three complement activation pathways were upregulated in MH compared to NMH but not in NMH compared with controls; immunohistochemistry confirmed complement deposition in MH exclusively. The expression of chemokines attracting neutrophil granulocytes as well as actual granulocyte infiltration were increased only in MH rats (CXCL6: 4.1-fold in MH over NMH).
Conclusion
The hypertensive kidney injury in malignant hypertension of 2K1C rats includes a robust expression and deposition of complement components as well as infiltration of neutrophil leukocytes, features which are not observed in the non-malignant course of renovascular hypertension. These pathways may contribute to the specific kidney injury observed in malignant hypertension.
Funding
- Government Support – Non-U.S.