Fiche publication


Date publication

juin 2021

Journal

International journal of molecular sciences

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOISBRUN Michel


Tous les auteurs :
Delaitre C, Boisbrun M, Lecat S, Dupuis F

Résumé

The physiological and pathophysiological relevance of the angiotensin II type 1 (AT) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin-angiotensin system and the AT 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 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 signaling and the development of biased AT agonists, able to selectively activate the β-arrestin transduction pathway rather than the G pathway, have led to new therapeutic strategies to target detrimental effects of AT activation. In this paper, we review the involvement of AT 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 agonists could be considered as new therapeutic avenues for cerebrovascular diseases.

Mots clés

AT1 receptor, Ang-(1–7), Angiotensin II, RAS, TRV023, TRV027, beta-arrestin, biased agonism, cerebrovascular disease

Référence

Int J Mol Sci. 2021 Jun 23;22(13):