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(Pro)renin receptor is thought to play a role in a wide range of biological processes, and recent studies have reported that (Pro)renin may have a function in pathophysiological conditions like retinopathy and pancreatic ductal adenocarcinoma.
(Pro)renin receptor is thought to play a role in a wide range of biological processes, and recent studies have reported that (Pro)renin may have a function in pathophysiological conditions like retinopathy and pancreatic ductal adenocarcinoma. It is thought that the soluble form of (Pro)renin may be a useful biomarker for disease.
A new study (Aliskiren reduces the release of soluble (pro)renin receptor from human umbilical vein endothelial cells: Biomedical Reports) looks at the effect of aliskiren, which is the first orally active direct renin inhibitor, on the protein levels of (Pro)renin.
Aliskiren and Renin Inhibition
Aliskiren is a prescription medication used to treat hypertension. It is an orally-active (nonpeptide) renin inhibitor that works by binding to the active site of human renin and inhibiting its activity. Studies have suggested that aliskiren reduces (Pro)renin expression in specific cases (the renal compartments of certain diabetic rats and cultured human aortic smooth muscle cells), but there is not much currently known about how aliskiren could impact the measurable concentration of soluble (Pro)renin in bodily fluids.
In Vitro Modeling
In this newest study, the team used cultured human umbilical vein endothelial cells (HUVECs) as an in vitro model for looking at how aliskiren would affect protein levels of both (Pro)renin and soluble (Pro)renin. In the course of their research, the scientists observed that exogenous prorenin was able to bind to the HUVEC membranes, and that this generated renin activity with full-length (Pro)renin expressed on the HUVEC cell surface.
When treated with aliskiren, the HUVECs showed decreased renin activity, confirming previous research indicating reduced cell-surface expression of full-length (Pro)renin with aliskiren treatment. The scientists note that an observed plateau in the level of per-cell renin activity could mean that there is a given level of full-length Pro(renin) on the cell membrane. The team also observed a reduction in the quantity of soluble (Pro)renin as a result of aliskiren treatment, which - to all appearances - seems to be the first report of aliskiren reducing the soluble form of (Pro)renin.
Using (Pro)renin Levels for Disease Diagnosis
These results suggest that, when using aliskiren to treat hypertension, the protein levels of soluble (Pro)renin could noticeably decline. Because of this, (Pro)renin and soluble (Pro)renin levels alone may not be sufficient for disease-monitoring purposes if aliskiren is also present.
Further research is needed to examine the effect of aliskiren on soluble (Pro)renin levels. It seems as though the quantity of soluble (Pro)renin depends on the extent that (Pro)renin is being produced and/or processed by the HUVECs used in this study, and additional clinical investigations could provide insight into the underlying mechanisms to clarify how aliskiren changes the quantity of soluble (Pro)renin. In the meantime, using soluble (Pro)renin as a potential disease biomarker may not be as effective during anti-hypertensive treatment with aliskiren.
Further Reading & References:
Yamashita, S., Biswas, K.B., Nabi, A.N., Nakagawa, T., Suzuki, F., & Ebihara, A. (1899). Aliskiren reduces the release of soluble (pro)renin receptor from human umbilical vein endothelial cells. Biomedical Reports, 0, 0-0. https://doi.org/10.3892/br.2018.1124
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