Involvement of A_2B adenosine receptors as anti-inflammatory in gestational diabesity

Pregnant women that are obese may develop gestational diabetes mellitus (GDM) configuring a new metabolic condition referred to as gestational diabesity. The metabolic alterations seen in gestational diabesity include a combination of an exacerbated pro-inflammatory state and fetoplacental endothelial dysfunction. Also, gestational diabesity associates with supra-physiological extracellular concentration of adenosine in the foetoplacental blood. Since adenosine plays a central role in the inflammatory response in GDM and obesity, it is likely that this nucleoside will play a similar role in gestational diabesity. However, the effect of adenosine in the foetoplacental vasculature in this condition is not yet addressed. Adenosine exerts its biological actions via four adenosine receptors. Activation of A_2B adenosine receptors (A_2BAR) subtype associates with an anti-inflammatory response in several tissue and diseases. In tissues from pregnant women with GDM, there is an overexpression of A_2BAR, and higher mRNA expression of ADORA2B (for A_2BAR) was shown to correlate with hyperglycaemia and oxidative stress. A_2BAR shows low affinity for adenosine (micromolar) and its activation results in triggering intracellular signalling cascades lowering the inflammatory response. This phenomenon requires a high level of extracellular adenosine in diseases of pregnancy such as GDM or gestational diabesity. In this review, we focused on the role of A_2BAR involvement in the biological actions of adenosine on inflammation in the foetoplacental vasculature in gestational diabesity. Some factors including oxidative stress and hypoxia in this phenomenon are discussed.