Dipyridamole, a compound that increases extracellular adenosine levels, as a preventive treatment for rheumatoid cachexia

Muscle decline due to chronic inflammation is a common condition in RA patients called rheumatoid cachexia (RC). Adenosine and ATP levels are essential in the control of myogenesis, anabolism/catabolism and senescence of muscle cells. Dipyridamole, an antiplatelet drug, is able to modulate adenosine levels in muscle cells and is an interesting therapeutic agent for RC. K/BxN mice model was treated with dipyridamole daily and sacrificed at the highest point of pawn inflammation. Cytokines arrays were performed in serum and muscle. Histology of TA and ankle was analyzed. Protein expression of myogenesis, purinergic system and senescence key markers were studied. Nucleotide content of GA was analyzed via HPLC. 2D and 3D culture models with C2C12 cells were performed to confirm the results obtained in mice model. RA mice developed weight loss, muscle size and activity decline and increment of senescence and atrophy. All this is dependent on the low adenosine levels and decreased expression of adenosine A2A/A2BR in RA muscle. Dipyridamole was able to prevent inflammation and muscle pathologies in RA mice due to adenosine and A2A/A2BR maintenance also cAMP/AMPK activation. This finding suggests dipyridamole is an interesting preventive drug to RA patients for counteracts RC development.