Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response

Abstract

Small-diameter vascular grafts (diameter <6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.

Adaptation process of decellularized vascular grafts as hemodialysis access in vivo

“…Current research findings indicate that both decellularized vascular grafts and HAVs are facing challenges such as rejection reactions, intimal hyperplasia, suboptimal revascularization and other issues [ 8 , 13 ]. Limited evidence suggests the involvement of immune cells, including macrophages, in the graft adaptation process in vivo [ 14 ]. Decellularized vascular grafts possess unique tissue structures [ 15 ], and it is still unknown whether the molecular mechanisms underlying intimal hyperplasia (or other phenomena) after their transplantation are consistent with those resulting from other pathological conditions such as arteriovenous fistulas (AVF), intimal injuries, and atherosclerosis.…”

Redefining vascular repair: revealing cellular responses on PEUU—gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models

“…Strategies involve growth factors like VEGF (vascular endothelial growth factor) and FGF (Fibroblast Growth Factor), promoting endothelial cell growth and migration. Moreover, nitric oxide compounds enhance endothelial function and inhibit platelets, while peptides like RGD (Arginylglycylaspartic acid) and REVD bind to integrins on endothelial progenitor cells ( Wang et al, 2015 ; Xie et al, 2022 ; Xue et al, 2019 ).…”

Injectable Near-Infrared Photothermal Responsive Drug-Loaded Multiwalled Carbon Nanotube Hydrogels for Spinal Cord Injury Repair

“…Vascular endothelial growth factor (VEGF) is an important growth factor, with a key role in endothelial cell growth and generation. Endothelial cells have multiple important roles in angiogenesis and are a key cell type for blood vessel formation and functional maintenance. , Therefore, the combination of PTX and VEGF in a hydrogel microsphere may create a better bionic microenvironment for spinal cord regeneration. However, if growth factors or drugs are released too quickly, then the effect of spinal cord regeneration may be compromised due to high local drug concentrations.…”