Interferon-Beta, a Decisive Factor in Angiogenesis and Arteriogenesis

Abstract

In this review we discuss the current literature on the effects of type I interferons (IFN) and their downstream effectors on vascular growth in experimental models in vitro and in vivo. In addition to its well-documented role in angiogenesis, that is, the growth of new capillaries from existing vessels, we will also describe emerging evidence and mechanisms by which type I IFN may inhibit arteriogenesis, that is, the expansive remodeling of existing collateral arteries. Crucial in both processes is the common role of circulating monocytes, which are known to act as pivotal cellular modulators in revascularization through secreted chemokines, proteases, and growth factors. These secreted molecules, which are all modulated by IFN signaling, act via degradation of the extracellular matrix and by stimulating the proliferation of vascular smooth muscle cells and endothelial cells. Thus, next to the antiviral and immunomodulatory activities of type I IFNs, a potent role of IFN-β as modulator of revascularization is now emerging and may be considered a potential clinical target for the stimulation of angiogenesis and arteriogenesis in ill-perfused tissues.

Vascular endothelial effects of collaborative binding to platelet/endothelial cell adhesion molecule-1 (PECAM-1)

“…Alternatively, the presence of physiologic blood flow may have significant crosstalk with antibody engagement of PECAM-1, which is itself a component of the endothelial mechanosensory complex 39 , and could negate some of the effects seen in other experimental settings. Of note, CEPAL antibodies did result in significant elevations of two pro-inflammatory cytokines, GM-CSF and IFN-β, both of which play significant roles in angiogenesis 40 , 41 . While of unclear significance, these cytokines and pro-angiogenic pathways will require close examination in future translational studies involving CEPAL-based therapies.…”

Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities

“…A recent study has also shown that Fli1 and its close homolog Erg1, transcriptionally control IFN-β gene in pulmonary ECs; thus, endothelial Fli1 and Erg1 deficiency leads to activation of IFN-β and its target genes in ECs (58). IFN-β is known to have potent anti-angiogenic effects (59).…”

Double-edged effects of interferons on the regulation of cancer-immunity cycle

“…165 In addition, treatment of endothelial cells with IFN-γ can selectively augment the migration of Th1 cells, the subtype of T cells that promotes cellular immunity. 166 Apart from endothelial cells, tumor vasculature also plays a crucial role in the process of trafficking and infiltration of T cells. However, IFNs, as anti-angiogenic cytokines, 167 may restrict the construction of vessels in the TME and thus make it difficult for T cell trafficking.…”

“…165 In addition, treatment of endothelial cells with IFN-γ can selectively augment the migration of Th1 cells, the subtype of T cells that promotes cellular immunity. 166 …”