Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus

Cardiovascular Diabetology

G. Pasterkamp¹  C. P. H. Lexis²  B. H. R. Wolffenbuttel³  I. C. C. van der Horst⁴  M. Reijrink⁵  H. van Goor⁵  L. M. Visser⁵  J. L. Hillebrands⁵  M. E. Lodewijk⁵  J. van Ark⁵  C. J. Zeebregts⁶  S. C. A. de Jager⁷ 

[1] Center Diagnostic Laboratory, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht University;Department of Cardiology, University of Groningen, University Medical Center Groningen;Department of Endocrinology, University of Groningen, University Medical Center Groningen;Department of Intensive Care Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University;Department of Pathology & Medical Biology - Pathology, University of Groningen, University Medical Center Groningen;Department of Surgery – Division of Vascular Surgery, University of Groningen, University Medical Center Groningen;Laboratory of Experimental Cardiology, University Medical Center Utrecht, University of Utrecht;

关键词: Angiogenesis;    Atherosclerosis;    Macrovascular disease;    Monocytes;    Monocyte heterogeneity;    Tie2;   

DOI  :  10.1186/s12933-022-01497-6

来源: DOAJ

【 摘 要 】

Abstract Background Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16−, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. Methods Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. Results Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM. Conclusions Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.

【 授权许可】

Unknown