Adenosine receptor signaling in vascular diseases: from molecular mechanisms to targeted therapeutics

Vascular diseases include disorders affecting arteries, veins, and capillaries, and remain the main cause of morbidity and mortality worldwide. The search for new therapeutic targets has led to the discovery of adenosine receptors as key regulators of the pathogenesis of several vascular conditions, including hypertension, atherosclerosis, abdominal aortic aneurysm, cerebral ischemia, and pathological angiogenesis. This review summarises the context-dependent functions of adenosine receptors in these diseases, with particular emphasis on mechanisms associated with endothelial-mesenchymal transition, vascular inflammation, and metabolic reprogramming. The therapeutic relevance of individual adenosine receptor subtypes is also discussed, including current preclinical evidence regarding receptor agonists and antagonists, as well as the potential value of combination-based approaches. Finally, current challenges and future research directions are considered, particularly the development of tissue-specific therapeutic strategies and the application of emerging technologies to improve the clinical translation of mechanistic findings.