,37 Despite these ambiguous data on its mode of action, a strong body of experimental and epidemiological evidence showed that both circulating and plaque levels of SPP1 are associated with plaque inflammation, instability and cardiovascular events,38 suggesting that combined effects of PHD2cko on macrophage apoptosis and fibroblasts may aggravate atherosclerosis. This evidence concerns the gene SPP1 and atherosclerosis.