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

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.