Increased amount of bone marrow-derived smooth muscle-like cells and accelerated atherosclerosis in diabetic apoE-deficient mice

AimsAtherosclerotic plaque development is accelerated in patients with diabetes. Bone marrow-derived smooth muscle-like cells have been detected in neointima and diabetes has a numerical and functional effect on circulating vascular progenitor cells. We hypothesized that an increased number of bone marrow-derived smooth muscle-like cells correlates with accelerated atherosclerosis in diabetic apoE-deficient mice.MethodsApoE−/− mice were subjected to total body irradiation and transplanted with bone marrow cells from GFP-transgenic mice. Mice were rendered diabetic by streptozotocin injection and examined after 4, 8, 11 and 15 weeks of diabetes.ResultsDiabetic mice showed a larger plaque area and a higher number of smooth muscle-like cells compared to non-diabetic mice at 11 and 15 weeks after diabetes induction. Bone marrow-derived smooth muscle-like cells were detected in atherosclerotic plaques of both diabetic and control mice, but numbers were higher in plaques of diabetic mice 11 weeks after induction of diabetes. The higher number of bone marrow-derived smooth muscle-like cells in plaque was associated with an increase in in vitro differentiation of smooth muscle-like cells from spleen mononuclear cells in diabetic mice.ConclusionsDiabetes increases the number of bone marrow-derived smooth muscle-like cells in atherosclerotic plaques and the differentiation of mononuclear cells towards smooth muscle-like cells, which may contribute to accelerated atherosclerotic plaque development in diabetic apoE−/− mice.

► Chimeric apoE−/− mice with GFP bone marrow were given STZ or vehicle injections. ► Atherosclerotic plaques were studied 4, 8, 11 and 15 weeks after onset of diabetes. ► Diabetes increased BM-derived smooth muscle-like cells in atherosclerotic plaques. ► Diabetes increased differentiation of MNC towards smooth muscle-like cells in vitro. ► Paracrine activity of SMLC may increase plaque size in diabetic atherosclerosis.