Key result
Angiotensin II drives an ~4-fold increase in mitochondrial depolarization in renal artery endothelial cells.
Why the study?
Continuous activation of angiotensin II induces renal vascular endothelial dysfunction, inflammation, and oxidative stress contributing to hypertensive nephropathy, but the molecular mechanisms involving miRNAs and mRNAs in renal artery endothelial cells remain unclear.
Absolute Event Rate: 17.99% vs 4.64%
p-value: p=<0.001
Hypothesis-generating for Ang II-mediated endothelial injury; requires human validation before any clinical consideration.
Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation and oxidative stress, all of which may contribute to renal damage. MicroRNAs (miRs/miRNAs) play a crucial regulatory role in the pathogenesis of hypertensive nephropathy (HN). The present study aimed to assess the differential expression profiles of potential candidate genes involved in Ang II-induced rat renal artery endothelial cell (RRAEC) dysfunction and explore their possible functions. In the present study, the changes in energy metabolism and autophagy function in RRAECs were evaluated using the Seahorse XF Glycolysis Stress Test and dansylcadaverine/transmission electron microscopy following exposure to Ang II. Subsequently, mRNA-miRNA sequencing experiments were performed to determine the differential expression profiles of mRNAs and miRNAs. Integrated bioinformatics analysis was applied to further explore the molecular mechanisms of Ang II on endothelial injury induced by Ang II. The present data supported the notion that Ang II upregulated glycolysis levels and promoted autophagy activation in RRAECs. The sequencing data demonstrated that 443 mRNAs and 58 miRNAs were differentially expressed (DE) in response to Ang II exposure, where 66 mRNAs and 55 miRNAs were upregulated, while 377 mRNAs and 3 miRNAs were downregulated (fold change >1.5 or <0.67; P<0.05). Functional analysis indicated that DE mRNA and DE miRNA target genes were mainly associated with cell metabolism (metabolic pathways), differentiation (Th1 and Th2 cell differentiation), autophagy (autophagy-animal and autophagy-other) and repair (RNA-repair). To the best of the authors' knowledge, this is the first report on mRNA-miRNA integrated profiles of Ang II-induced RRAECs. The present results provided evidence suggesting that the miRNA-mediated effect on the 'mTOR signaling pathway' might play a role in Ang II-induced RRAEC injury by driving glycolysis and autophagy activation. Targeting miRNAs and their associated pathways may provide valuable insight into the clinical management of HN and may improve patient outcome.
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Liu et al. (2020) studied Hypertensive nephropathy (Renal artery endothelial cell dysfunction). Angiotensin II vs. Untreated RRAECs was evaluated on Proportion of cells with decreased mitochondrial membrane potential (F value) (p=<0.001). Angiotensin II exposure in rat renal artery endothelial cells significantly decreased mitochondrial membrane potential, upregulated glycolysis and autophagy, and induced the differential expression of 443 mRNAs and 58 miRNAs.
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