The Role of Complement in Angiogenesis

Abstract

The link of the complement system to angiogenesis has remained circumstantial and speculative for several years. Perhaps the most clinically relevant example of possible involvement of complement in pathological neovascularization is age-related macular degeneration. Recent studies, however, provide more direct and experimental evidence that indeed the complement system regulates physiological and pathological angiogenesis in models of wound healing, retinal regeneration, age-related macular degeneration, and cancer. Interestingly, complement-dependent mechanisms involved in angiogenesis are very much context dependent, including anti- and proangiogenic functions. Here, we discuss these new developments that place complement among other important regulators of homeostatic and pathological angiogenesis, and we provide the perspective on how these newly discovered complement functions can be targeted for therapy.

Cooperation between Angiogenesis, Vasculogenesis, Chemotaxis, and Coagulation in Breast Cancer Metastases Development: Pathophysiological Point of View

“…Presence of receptors for VEGF on BC cells is linked to cancer cells proliferation, survival, migration, adhesion, and invasion as a result of autocrine signaling pathway activation [ 45 ]. Interestingly, in small metastatic lesions the extensive activation of proangiogenic factors—the angiogenic switch—is necessary for the progression of small avascular micrometastases to macrometastases and thus escaping of cancer cells from dormancy [ 46 ]. The soluble form of VEGFR1 (sVEGFR1), which is a product of the short mRNA transcript of the VEGFR1 gene, impairs angiogenesis—it binds to VEGF-A, thus preventing it from binding to VEGFR1 or VEGFR2 on ECs and inhibiting signal transduction [ 40 , 42 ].…”

The Onset of Whole-Body Regeneration in Botryllus schlosseri: Morphological and Molecular Characterization

“…Correct regeneration of lost organs in vertebrates necessitates a finely tuned interplay between inflammatory response, neovascularization and ECM remodeling to recruit stem/progenitor cells to the regenerative area and to organize the rebuilding tissues (reviewed in Mastellos et al, 2013 ). For instance, beyond its role as sentinels of immunity, C3 stimulate retina regeneration in chicken and mice ( Haynes et al, 2013 ; Peterson et al, 2021 ), while in mouse complement proteins regulate wound-healing and angiogenesis in a complex, not fully resolved manner (reviewed in Markiewski et al, 2020 ). In ascidians, C3 expression has been reported in various epithelial cells and hemocytes of several species ( Pinto et al, 2003 ; Raftos et al, 2004 ; Giacomelli et al, 2012 ).…”

The onset of whole-body regeneration inBotryllus schlosseri: morphological and molecular characterization

“…For instance, beyond its role as sentinels of immunity, C3 stimulate retina regeneration in chicken and mice (Haynes et al, 2013;Peterson et al, 2021), while in mouse complement proteins regulate woundhealing and angiogenesis in a complex, not fully resolved manner (reviewed in Markiewski et al, 2020). In ascidians, C3 expression has been reported in various epithelial cells and hemocytes of several species (Pinto et al, 2003;Raftos et al, 2004;Giacomelli et al, 2012).…”