Adenosine A_2A receptor activation prevents DOCA-salt induced hypertensive cardiac remodeling via iBAT

Area of Science:

• Cardiovascular Research
• Pharmacology
• Metabolic Disease

Background:

• Hypertensive cardiac remodeling involves cardiomyocyte hypertrophy, death, and fibrosis.
• Adenosine receptors, including A_2AR, are present in the cardiovascular system, but their role in hypertension-induced cardiac remodeling is unclear.

Purpose of the Study:

• To investigate the role of adenosine A_2A receptor (A_2AR) activation in mitigating cardiac remodeling associated with hypertension.
• To explore the underlying mechanisms, including the involvement of brown adipose tissue (BAT) and fibroblast growth factor 21 (FGF21).

Main Methods:

• Wild-type mice were subjected to DOCA-salt treatment to induce hypertension.
• Mice received either an A_2AR agonist (CGS21680) or antagonist (KW6002).
• Echocardiography assessed cardiac function; histological analysis evaluated hypertrophy, inflammation, and fibrosis. BAT depletion surgery was performed in some groups.

Main Results:

• A_2AR agonist CGS21680 improved cardiac dysfunction, reduced cardiomyocyte hypertrophy, cardiac inflammation, and fibrosis in DOCA-salt mice.
• The protective effects of CGS21680 were abolished in mice with depleted BAT.
• CGS21680 treatment increased the levels of BAT-derived fibroblast growth factor 21 (FGF21).

Conclusions:

• Activation of A_2AR demonstrates a protective effect against cardiac remodeling in hypertension.
• This cardioprotection is dependent on intact brown adipose tissue and is associated with increased FGF21 production.
• Targeting A_2AR may represent a novel therapeutic strategy for managing heart damage in hypertensive individuals.