Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells
Introduction : The recent discovery of a specific receptor for renin/prorenin (PRR) has added new interest to the potential pharmacological actions of aliskiren, the first direct renin inhibitor. Materials and methods : In the present study, to gain new insights into the pharmacological properties o...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2011-12-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320311408751 |
| _version_ | 1797285704131149824 |
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| author | Nicola Ferri Carolina Magdalen Greco Giuseppe Maiocchi Alberto Corsini |
| author_facet | Nicola Ferri Carolina Magdalen Greco Giuseppe Maiocchi Alberto Corsini |
| author_sort | Nicola Ferri |
| collection | DOAJ |
| description | Introduction : The recent discovery of a specific receptor for renin/prorenin (PRR) has added new interest to the potential pharmacological actions of aliskiren, the first direct renin inhibitor. Materials and methods : In the present study, to gain new insights into the pharmacological properties of aliskiren, we investigated the effect of aliskiren on PRR expression and activity in cultured human smooth muscle cells (HSMCs). Results : Co-incubation of HSMCs with angiotensinogen (ANG) (1.5× 10 -7 M) and prorenin (10 -8 –10 -7 M) resulted in an efficient production (within 4h) of angiotensin I, almost completely inhibited by 10 -5 M aliskiren (-86.0 ± 14.0%). In HSMCs stimulated with both ANG and prorenin, a 24h incubation with aliskiren (10 -6 –10 -5 M) resulted in a concentration-dependent reduction of PRR mRNA levels (IC 50 4.6 × 10 -6 M). The cell surface expression of PRR determined by flow cytometry analysis was also reduced after incubation with aliskiren in a concentration-dependent manner. The lower levels of PRR were associated with a reduced expression of TGF-β, PAI-1 and type I collagen mRNA. Conclusions : These results suggest a direct pharmacological action of aliskiren on PRR expression and its signalling pathway in HSMCs. This reported action of aliskiren may reveal a new scenario of the pharmacological properties of aliskiren. |
| first_indexed | 2024-03-07T18:07:05Z |
| format | Article |
| id | doaj.art-f4e7a6ba02b1475393c7823680c95faa |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T18:07:05Z |
| publishDate | 2011-12-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-f4e7a6ba02b1475393c7823680c95faa2024-03-02T09:11:10ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762011-12-011210.1177/1470320311408751Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cellsNicola Ferri0Carolina Magdalen Greco1Giuseppe Maiocchi2Alberto Corsini3Department of Pharmacological Sciences, University of Milan, ItalyDepartment of Pharmacological Sciences, University of Milan, ItalyNovartis Farma S.p.A. Medical Department, Origgio ItalyDepartment of Pharmacological Sciences, University of Milan, ItalyIntroduction : The recent discovery of a specific receptor for renin/prorenin (PRR) has added new interest to the potential pharmacological actions of aliskiren, the first direct renin inhibitor. Materials and methods : In the present study, to gain new insights into the pharmacological properties of aliskiren, we investigated the effect of aliskiren on PRR expression and activity in cultured human smooth muscle cells (HSMCs). Results : Co-incubation of HSMCs with angiotensinogen (ANG) (1.5× 10 -7 M) and prorenin (10 -8 –10 -7 M) resulted in an efficient production (within 4h) of angiotensin I, almost completely inhibited by 10 -5 M aliskiren (-86.0 ± 14.0%). In HSMCs stimulated with both ANG and prorenin, a 24h incubation with aliskiren (10 -6 –10 -5 M) resulted in a concentration-dependent reduction of PRR mRNA levels (IC 50 4.6 × 10 -6 M). The cell surface expression of PRR determined by flow cytometry analysis was also reduced after incubation with aliskiren in a concentration-dependent manner. The lower levels of PRR were associated with a reduced expression of TGF-β, PAI-1 and type I collagen mRNA. Conclusions : These results suggest a direct pharmacological action of aliskiren on PRR expression and its signalling pathway in HSMCs. This reported action of aliskiren may reveal a new scenario of the pharmacological properties of aliskiren.https://doi.org/10.1177/1470320311408751 |
| spellingShingle | Nicola Ferri Carolina Magdalen Greco Giuseppe Maiocchi Alberto Corsini Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells Journal of the Renin-Angiotensin-Aldosterone System |
| title | Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells |
| title_full | Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells |
| title_fullStr | Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells |
| title_full_unstemmed | Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells |
| title_short | Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells |
| title_sort | aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells |
| url | https://doi.org/10.1177/1470320311408751 |
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