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Thromb Haemost 2023; 123(10): 989-998
DOI: 10.1055/s-0043-1768162
Atherosclerosis and Ischaemic Disease

Adventitial Vasa Vasorum Neovascularization in Femoral Artery of Type 2 Diabetic Patients with Macroangiopathy Is Associated with Macrophages and Lymphocytes as well as the Occurrence of Cardiovascular Events

Dong Chen‡   *
1   Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China
,
Zixi Zhao‡   *
2   NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People's Republic of China
,
Peng Liu
3   Department of Surgery, Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin, People's Republic of China
,
Xinbang Liu
2   NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People's Republic of China
,
Xin Wang
4   School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China
,
Qiuyue Ren
5   Department of Endocrinology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
,
Bai Chang
2   NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People's Republic of China
› Author Affiliations
Funding This work was supported by the National Natural Science Foundation of China (81973614).
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Abstract

Objectives This study was conducted to assess the relationship between adventitial vasa vasorum neovascularization (VVn) in femoral artery of type 2 diabetic patients with macroangiopathy and the recruitment of macrophages and lymphocytes, and to relate the density of VVn to the occurrence of cardiovascular events.

Materials Femoral artery samples were obtained from amputation cases. A total of 55 type 2 diabetic patients with macroangiopathy, 15 autopsy cases with type 2 diabetes without atherosclerosis.

Methods Hematoxylin and eosin (H&E) staining to observe the histopathological features; Victoria blue staining to analyze the histological features; immunohistochemistry (CD34, CD68, CD20, and CD3) to determine the VVn density and the expression of macrophages, B lymphocytes, and T lymphocytes.

Results Type 2 diabetic patients with macroangiopathy showed a higher mean adventitial VVn density in femoral artery (48.40 ± 9.39 no./mm2) than patients with type 2 diabetes without atherosclerosis (19.75 ± 6.28 no./mm2) (p < 0.01). In addition, the VVn density was positively associated with the expression of CD68 macrophages (r = 0.62, p < 0.01) and CD20 B lymphocytes (r = 0.59, p < 0.01). Type 2 diabetic patients with high VVn density showed more adverse cardiovascular events (27/35 vs. 8/20 events, p = 0.006). In multivariable analysis adjusted for main risk factors for cardiovascular disease, VVn was still independently associated with adverse cardiovascular events (p = 0.01).

Conclusion VVn density in type 2 diabetic patients with macroangiopathy is positively correlated with the adventitial immune-inflammatory cell numbers and the development of atherosclerotic lesions. Furthermore, VVn density is associated with adverse cardiovascular events.

Keywords

vasa vasorum - diabetic macroangiopathy - atherosclerosis - lymphocytes - macrophages - cardiovascular events

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.


Ethical Approval Statement

The study was approved by the Ethics Committee of Tianjin Medical University Chu Hsien-I Memorial Hospital (DXBYYhMEC2018–13), and all participants and their parent(s)/guardian(s) signed informed consent prior to the participation.


Authors' Contribution

D.C. and Z.Z. analyzed the data and wrote the manuscript. X.L. and P.L. collected the data and tissue. X.W. contributed to the discussion and commented on the manuscript. D.C. and Q.R. developed the protocol and performed statistical analyses. Q.R. performed the pathological analysis. D.C., Q.R., and B.C. conceived the study design and revised the manuscript. D.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.


* Contributed equally to this study.


Supplementary Material



Publication History

Received: 14 December 2022

Accepted: 09 March 2023

Article published online:
10 April 2023

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