PMID- 35549955
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20220716
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 21
IP  - 1
DP  - 2022 May 12
TI  - Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) 
      expressing monocytes in individuals with type 2 diabetes mellitus.
PG  - 72
LID - 10.1186/s12933-022-01497-6 [doi]
LID - 72
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Reijrink, M
AU  - Reijrink M
AD  - Department of Pathology & Medical Biology - Pathology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, The 
      Netherlands.
AD  - Department of Internal Medicine - Division of Vascular Medicine, University of 
      Groningen, University Medical Center Groningen, Groningen, The Netherlands.
FAU - van Ark, J
AU  - van Ark J
AD  - Department of Pathology & Medical Biology - Pathology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, The 
      Netherlands.
FAU - Lexis, C P H
AU  - Lexis CPH
AD  - Department of Cardiology, University of Groningen, University Medical Center 
      Groningen, Groningen, The Netherlands.
FAU - Visser, L M
AU  - Visser LM
AD  - Department of Pathology & Medical Biology - Pathology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, The 
      Netherlands.
FAU - Lodewijk, M E
AU  - Lodewijk ME
AD  - Department of Pathology & Medical Biology - Pathology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, The 
      Netherlands.
FAU - van der Horst, I C C
AU  - van der Horst ICC
AD  - Department of Intensive Care Medicine, Cardiovascular Research Institute 
      Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
AD  - Department of Intensive Care Medicine, Maastricht University Medical Center, 
      Maastricht, The Netherlands.
FAU - Zeebregts, C J
AU  - Zeebregts CJ
AD  - Department of Surgery - Division of Vascular Surgery, University of Groningen, 
      University Medical Center Groningen, Groningen, The Netherlands.
FAU - van Goor, H
AU  - van Goor H
AD  - Department of Pathology & Medical Biology - Pathology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, The 
      Netherlands.
FAU - de Jager, S C A
AU  - de Jager SCA
AD  - Laboratory of Experimental Cardiology, University Medical Center Utrecht, 
      University of Utrecht, Utrecht, The Netherlands.
FAU - Pasterkamp, G
AU  - Pasterkamp G
AD  - Center Diagnostic Laboratory, Division Laboratories and Pharmacy, University 
      Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
FAU - Wolffenbuttel, B H R
AU  - Wolffenbuttel BHR
AD  - Department of Endocrinology, University of Groningen, University Medical Center 
      Groningen, Groningen, The Netherlands.
FAU - Hillebrands, J L
AU  - Hillebrands JL
AD  - Department of Pathology & Medical Biology - Pathology, University of Groningen, 
      University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, The 
      Netherlands. j.l.hillebrands@umcg.nl.
LA  - eng
PT  - Journal Article
DEP - 20220512
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Angiopoietin-1)
RN  - 0 (Angiopoietin-2)
RN  - EC 2.7.10.1 (Receptor, TIE-2)
RN  - EC 2.7.10.1 (TEK protein, human)
SB  - IM
MH  - Angiopoietin-1/metabolism
MH  - Angiopoietin-2/metabolism
MH  - *Atherosclerosis/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Humans
MH  - Monocytes/metabolism
MH  - *Plaque, Atherosclerotic/pathology
MH  - Receptor, TIE-2
MH  - Tunica Intima/chemistry/metabolism/pathology
PMC - PMC9102255
OTO - NOTNLM
OT  - Angiogenesis
OT  - Atherosclerosis
OT  - Macrovascular disease
OT  - Monocyte heterogeneity
OT  - Monocytes
OT  - Tie2
OT  - Type 2 diabetes mellitus
COIS- The authors declare that they have no competing interests.
EDAT- 2022/05/14 06:00
MHDA- 2022/05/18 06:00
PMCR- 2022/05/12
CRDT- 2022/05/13 12:16
PHST- 2021/12/29 00:00 [received]
PHST- 2022/02/18 00:00 [accepted]
PHST- 2022/05/13 12:16 [entrez]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/05/12 00:00 [pmc-release]
AID - 10.1186/s12933-022-01497-6 [pii]
AID - 1497 [pii]
AID - 10.1186/s12933-022-01497-6 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2022 May 12;21(1):72. doi: 10.1186/s12933-022-01497-6.