Role of proangiogenic Tie2+ monocytes (TEMs) in diabetes-associated macrovascular disease.

Ffocus is on the role of adipose tissue inflammation/dysfunction on the development of vascular stiffness and calcification in T2D and CKD. Related to this central theme previously is performed a patient-related study in which monocyte subset frequencies were determined in subjects with T2D with or without macro-vascular disease (i.e. peripheral artery disease [PAD] and coronary artery disease [CAD]). In this study we observed increased numbers of Tie2+ monocytes (TEMs) within the population of CD14+CD16+ intermediate monocytes. Based on this observation we hypothesize that T2D is associated with increased numbers of TEMs that may subsequently migrate into developing atherosclerotic plaques. As TEMs are pro-angiogenic, intra-plaque recruitment of TEMs might result in enhanced angiogenesis thereby contributing to increased plaque vulnerability. To finalize this study, immunohistochemistry for Tie2-expressing cells need to be performed on atherosclerotic tissue. Staining procedure has been established and plaque tissue is available. As angiopoietin (Ang) 1 and 2 are the ligands for Tie2, levels of circulating Ang1 and Ang2 will be determined in archival plasma samples using a commercially available kit. Required stainings and ELISAs will be performed and to revise the draft manuscript.

We hypothesize that the subpopulation of CD68+Tie2+ macrophages is increased in diabetic patients in comparison to non-diabetic individuals. These macrophages may cause an increased expression of Ang2 in plaques, thereby enhancing angiogenesis which contributes to increased plaque vulnerability.

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