Aortic valve calcification was evaluated in atherosclerotic prone ApoE<sup>-/-</sup> mice or in mice with dual deficiencies of ApoE and RAGE (ApoE<sup>-/-</sup>RAGE<sup>-/-</sup>) fed with high cholesterol diet for 24weeks.
Our study is also the first to establish a distinct role of hyperglycemia and hypercholesterolemia in osteochondrogenic differentiation of SMCs and determined these cells as a major source contributing to cartilaginous and calcifying lesions of T2DM blood vessels, possibly mediated by RAGE.