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

• Published in: Atherosclerosis Vol. 226; no. 2; pp. 341 - 347
• Main Authors: Fledderus, J.O, van Oostrom, O, de Kleijn, D.P.V, den Ouden, K, Penders, A.F, Gremmels, H, de Bree, P, Verhaar, M.C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.02.2013; Elsevier
• Subjects: Animals; Apolipoproteins E - deficiency; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - pathology; Atherosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Bone marrow; bone marrow cells; Bone Marrow Cells - cytology; Bone Marrow Transplantation; Cardiology. Vascular system; Cardiovascular; Cell Differentiation; Diabetes; Diabetes Mellitus, Experimental - pathology; Fundamental and applied biological sciences. Psychology; irradiation; Male; Medical sciences; Mice; Mice, Transgenic; Myocytes, Smooth Muscle - cytology; patients; Plaque, Atherosclerotic - pathology; Smooth muscle-like cells; spleen; stem cells; streptozotocin; Vertebrates: cardiovascular system; Bone marrow; Diabetes; Smooth muscle-like cells; Atherosclerosis; Endocrinopathy; Diabetes mellitus; Rodentia; Smooth muscle; Cardiovascular disease; Vascular disease; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.11.017

Abstract Aims Atherosclerotic 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. Methods ApoE−/− 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. Results Diabetic 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. Conclusions Diabetes 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.