Targeting Adenosine Receptors for the Treatment of Cardiac Fibrosis

Frontiers in Pharmacology
Elizabeth A VecchioLauren T May

Abstract

Adenosine is a ubiquitous molecule with key regulatory and cytoprotective mechanisms at times of metabolic imbalance in the body. Among a plethora of physiological actions, adenosine has an important role in attenuating ischaemia-reperfusion injury and modulating the ensuing fibrosis and tissue remodeling following myocardial damage. Adenosine exerts these actions through interaction with four adenosine G protein-coupled receptors expressed in the heart. The adenosine A2B receptor (A2BAR) is the most abundant adenosine receptor (AR) in cardiac fibroblasts and is largely responsible for the influence of adenosine on cardiac fibrosis. In vitro and in vivo studies demonstrate that acute A2BAR stimulation can decrease fibrosis through the inhibition of fibroblast proliferation and reduction in collagen synthesis. However, in contrast, there is also evidence that chronic A2BAR antagonism reduces tissue fibrosis. This review explores the opposing pro- and anti-fibrotic activity attributed to the activation of cardiac ARs and investigates the therapeutic potential of targeting ARs for the treatment of cardiac fibrosis.

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Citations

Oct 24, 2017·The Journal of Pharmacy and Pharmacology·Amirhossein BahreyniSeyed M Hassanian
Dec 20, 2017·Frontiers in Pharmacology·Allan K N AlencarGisele Zapata-Sudo
Apr 22, 2018·British Journal of Pharmacology·Elizabeth A VecchioLauren T May
Nov 2, 2018·Cardiovascular Toxicology·Leslie C ThompsonChristopher J Wingard
Jul 22, 2018·Circulation·Toru HashimotoDavid A Kass
Jan 1, 2020·Cells·Marion DelaunayDario Diviani
Sep 25, 2019·Journal of Cardiovascular Development and Disease·Jianlin FengLixia Yue
Sep 30, 2020·Cardiovascular Research·Franck PaganelliRégis Guieu
Apr 30, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Julia HesseJürgen Schrader
Oct 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Barbara Kutryb-ZajacRyszard T Smolenski
Aug 28, 2021·International Journal of Molecular Sciences·Rebecca SohnZsuzsa Jenei-Lanzl
Jul 4, 2018·Journal of Medicinal Chemistry·Lucienne Juillerat-JeanneretDela Golshayan

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Methods Mentioned

BETA
antisense oligonucleotide A
transgenic

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