Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes
The physiological and pathophysiological relevance of the angiotensin II type 1 (AT<sub>1</sub>) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT<sub>1</sub> receptor are the targets of several class...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/13/6738 |
| _version_ | 1797529106219270144 |
|---|---|
| author | Céline Delaitre Michel Boisbrun Sandra Lecat François Dupuis |
| author_facet | Céline Delaitre Michel Boisbrun Sandra Lecat François Dupuis |
| author_sort | Céline Delaitre |
| collection | DOAJ |
| description | The physiological and pathophysiological relevance of the angiotensin II type 1 (AT<sub>1</sub>) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT<sub>1</sub> receptor are the targets of several classes of therapeutics (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, ARBs) used as first-line treatments in cardiovascular diseases. The importance of AT<sub>1</sub> in the regulation of the cerebrovascular system is also acknowledged. However, despite numerous beneficial effects in preclinical experiments, ARBs do not induce satisfactory curative results in clinical stroke studies. A better understanding of AT<sub>1</sub> signaling and the development of biased AT<sub>1</sub> agonists, able to selectively activate the β-arrestin transduction pathway rather than the G<sub>q</sub> pathway, have led to new therapeutic strategies to target detrimental effects of AT<sub>1</sub> activation. In this paper, we review the involvement of AT<sub>1</sub> in cerebrovascular diseases as well as recent advances in the understanding of its molecular dynamics and biased or non-biased signaling. We also describe why these alternative signaling pathways induced by β-arrestin biased AT<sub>1</sub> agonists could be considered as new therapeutic avenues for cerebrovascular diseases. |
| first_indexed | 2024-03-10T10:08:42Z |
| format | Article |
| id | doaj.art-a43d1f34e76f4fc5a3847e1d8f5a6c73 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:08:42Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a43d1f34e76f4fc5a3847e1d8f5a6c732023-11-22T01:22:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213673810.3390/ijms22136738Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New HopesCéline Delaitre0Michel Boisbrun1Sandra Lecat2François Dupuis3CITHEFOR, Université de Lorraine, F-54000 Nancy, FranceCNRS, L2CM, Université de Lorraine, F-54000 Nancy, FranceBiotechnologie et Signalisation Cellulaire, UMR7242 CNRS/Université de Strasbourg, 300 Boulevard Sébastien Brant, CS 10413, CEDEX, 67412 Illkirch-Graffenstaden, FranceCITHEFOR, Université de Lorraine, F-54000 Nancy, FranceThe physiological and pathophysiological relevance of the angiotensin II type 1 (AT<sub>1</sub>) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT<sub>1</sub> receptor are the targets of several classes of therapeutics (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, ARBs) used as first-line treatments in cardiovascular diseases. The importance of AT<sub>1</sub> in the regulation of the cerebrovascular system is also acknowledged. However, despite numerous beneficial effects in preclinical experiments, ARBs do not induce satisfactory curative results in clinical stroke studies. A better understanding of AT<sub>1</sub> signaling and the development of biased AT<sub>1</sub> agonists, able to selectively activate the β-arrestin transduction pathway rather than the G<sub>q</sub> pathway, have led to new therapeutic strategies to target detrimental effects of AT<sub>1</sub> activation. In this paper, we review the involvement of AT<sub>1</sub> in cerebrovascular diseases as well as recent advances in the understanding of its molecular dynamics and biased or non-biased signaling. We also describe why these alternative signaling pathways induced by β-arrestin biased AT<sub>1</sub> agonists could be considered as new therapeutic avenues for cerebrovascular diseases.https://www.mdpi.com/1422-0067/22/13/6738AT<sub>1</sub> receptorAngiotensin IIcerebrovascular diseasebiased agonismbeta-arrestinRAS |
| spellingShingle | Céline Delaitre Michel Boisbrun Sandra Lecat François Dupuis Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes International Journal of Molecular Sciences AT<sub>1</sub> receptor Angiotensin II cerebrovascular disease biased agonism beta-arrestin RAS |
| title | Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes |
| title_full | Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes |
| title_fullStr | Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes |
| title_full_unstemmed | Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes |
| title_short | Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes |
| title_sort | targeting the angiotensin ii type 1 receptor in cerebrovascular diseases biased signaling raises new hopes |
| topic | AT<sub>1</sub> receptor Angiotensin II cerebrovascular disease biased agonism beta-arrestin RAS |
| url | https://www.mdpi.com/1422-0067/22/13/6738 |
| work_keys_str_mv | AT celinedelaitre targetingtheangiotensiniitype1receptorincerebrovasculardiseasesbiasedsignalingraisesnewhopes AT michelboisbrun targetingtheangiotensiniitype1receptorincerebrovasculardiseasesbiasedsignalingraisesnewhopes AT sandralecat targetingtheangiotensiniitype1receptorincerebrovasculardiseasesbiasedsignalingraisesnewhopes AT francoisdupuis targetingtheangiotensiniitype1receptorincerebrovasculardiseasesbiasedsignalingraisesnewhopes |