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Circulating prorenin: its molecular forms and plasma concentrations

Abstract

The renin-angiotensin-aldosterone system plays pivotal roles in the maintenance of fluid homeostasis and in the pathophysiology of major human diseases. However, the molecular forms of plasma renin/prorenin have not been fully elucidated, and measurements of plasma prorenin levels are still unavailable for clinical practice. We attempted to evaluate the molecular forms of human plasma prorenin and to directly measure its concentration without converting it to renin to determine its activity. Polyacrylamide gel electrophoresis and subsequent immunoblotting using antibodies that specifically recognise prosegment sequences were used to analyse its molecular forms in plasma. We also created a sandwich enzyme-linked immunosorbent assay suitable for directly quantifying the plasma concentration. The plasma level in healthy people was 3.0–13.4 μg/mL, which is from 3 to 4 orders of magnitude higher than the levels reported thus far. Plasma immunoreactive prorenin consists of three major distinct components: a posttranslationally modified full-length protein, an albumin-bound form and a smaller protein truncated at the common C-terminal renin/prorenin portion. In contrast to plasma renin activity, plasma prorenin concentrations were not affected by the postural changes of the donor. Hence, plasma prorenin molecules may be posttranslationally modified/processed or bound to albumin and are present in far higher concentrations than previously thought.

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Acknowledgements

The authors thank Rika Kato and Yukiko Kato for their technical assistance. We thank Edanz Group for editing a draft of this paper.

Funding

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to MS (18H05383 and 20K20389), YKo (17K19926 and 17H02206) and KF (18K15431).

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Correspondence to Masayoshi Shichiri.

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Fujimoto, K., Kawamura, S., Bando, S. et al. Circulating prorenin: its molecular forms and plasma concentrations. Hypertens Res 44, 674–684 (2021). https://doi.org/10.1038/s41440-020-00610-0

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