Abstract
Angiogenesis is a vital biological process, and neovascularization is essential for the development, wound repair, and perfusion of ischemic tissue. Neovascularization and inflammation are independent biological processes that are linked in response to injury and ischemia. While clear that pro-inflammatory factors drive angiogenesis, the role of anti-inflammatory interleukins in angiogenesis remains less defined. An interleukin with anti-inflammatory yet pro-angiogenic effects would hold great promise as a therapeutic modality to treat many disease states where inflammation needs to be limited, but revascularization and reperfusion still need to be supported. As immune modulators, interleukins can polarize macrophages to a pro-angiogenic and reparative phenotype, which indirectly influences angiogenesis. Interleukins could also potentially directly induce angiogenesis by binding and activating its receptor on endothelial cells. Although a great deal of attention is given to the negative effects of pro-inflammatory interleukins, less is described concerning the potential protective effects of anti-inflammatory interleukins on various disease processes. To focus this review, we will consider IL-4, IL-10, IL-13, IL-19, and IL-33 to be anti-inflammatory interleukins, all of which have recognized immunomodulatory effects. This review will summarize current research concerning anti-inflammatory interleukins as potential drivers of direct and indirect angiogenesis, emphasizing their role in future therapeutics.
Highlights
Sprouting angiogenesis is the expansion of new blood vessels from pre-existing vasculature where tip cells are stimulated to express proteases, migrate, proliferate, and form new tubes [1,2]
M2 macrophages express a significant number of soluble angiogenic factors such as vascular endothelial growth factors (VEGFs)-A, TGFα, and PDGF-β, which act in a paracrine manner to promote wound repair and neovascularization on local endothelial cells [20,22]
These macrophage-derived cytokines can elicit the pro-angiogenic processes on endothelial cell (EC) outlined in the previous section
Summary
Sprouting angiogenesis is the expansion of new blood vessels from pre-existing vasculature where tip cells are stimulated to express proteases, migrate, proliferate, and form new tubes [1,2]. Pathological angiogenesis is often the target of anti-tumor therapy as it contributes to tumor growth and metastasis [1,12] Tissue hypoxia initiates both inflammatory and angiogenic factors to promote angiogenesis in an attempt to restore perfusion, and, as with any complex process, revascularization of ischemic tissue involves multiple cell types. Lindau tumor suppressor protein (pVHL), leading to polyubiquitination and proteasomal of HIF-1α [18] In this way, low levels of HIF-1α ensure minimal angiogenesis under degradation of HIF‐1α [18]. Tration rises, leading to reduced HIF‐1α stability and activity, ending the angiogenic process [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
