Vascular endothelial growth factor-D expression in human atherosclerotic lesions

Abstract

Our results suggest that in large arteries VEGF-D is mainly expressed in smooth muscle cells and that it may have a role in the maintenance of vascular homeostasis. However, in complicated lesions it was also expressed in macrophages and may contribute to plaque neovascularization. The constitutive expression of VEGFR-2 in arteries suggests that it may be one of the principal mediators of the VEGF-D effects in large arteries.

Gene transfer using the mature form of VEGF-D reduces neointimal thickening through nitric oxide-dependent mechanism

“…4,15 VEGF-D is constitutively expressed in normal human arteries and early-stage atherosclerosis, but the expression is decreased and its biological processing to the mature form is disturbed in connective tissue-rich atherosclerotic lesions. 10 Consequently, the vasculoprotective effects of VEGF-D may be decreased in end-stage atherosclerotic lesions that are candidates for PT(C)A. In this study, we tested the hypothesis that intra-arterial gene transfer using the mature form of VEGF-D could be protective and prevent restenosis.…”

“…8,9 In human atherosclerosis VEGF-D is present throughout the lesion development, but its amounts are reduced in complicated lesions. 10 Furthermore, in complicated lesions most of the VEGF-D appears to be intracellular and not effectively processed into its extracellular mature form. 10 Thus, gene transfer using the secreted proteolytically processed biologically active form of VEGF-D, VEGF-D DNDC , could have beneficial effects on the treatment of postangioplasty restenosis.…”

Angiogenesis in Atherogenesis

“…60 -65 Of biological significance, atherosclerotic plaques also express VEGF receptors. 64,65 VEGF-R2 is considered to be the central mediator of endothelial cell proliferation in angiogenesis and mediates VEGF-induced adhesion molecule expression and vascular permeability. 66,67 VEGF-R1 is of significance for macrophage infiltration and activation, which may ultimately influence angiogenesis.…”

Gene Transfers of Vascular Endothelial Growth Factor-A, Vascular Endothelial Growth Factor-B, Vascular Endothelial Growth Factor-C, and Vascular Endothelial Growth Factor-D Have No Effects on Atherosclerosis in Hypercholesterolemic Low-Density Lipoprotein-Receptor/Apolipoprotein B48-Deficient Mice

“…2,3 Also, VEGF-D is expressed in normal human arteries and atherosclerotic lesions. 4 VEGF-A has been proposed to have several roles in the arterial wall: it can be protective by increasing the production of nitric oxide and prostacyclin 5 and by lowering LDL toxicity. 6 It has also been shown to mediate antiapoptotic effects in endothelium.…”