Connexins and angiogenesis: Functional aspects, pathogenesis, and emerging therapies (Review)

Abstract

connexins (cxs) play key roles in cellular communication. By facilitating metabolite exchange or interfering with distinct signaling pathways, cxs affect cell homeostasis, proliferation, and differentiation. Variations in the activity and expression of cxs have been linked to numerous clinical conditions including carcinomas, cardiac disorders, and wound healing. Recent discoveries on the association between cxs and angiogenesis have sparked interest in cx-mediated angiogenesis due to its essential functions in tissue formation, wound repair, tumor growth, and metastasis. It is now widely recognized that understanding the association between cxs and angiogenesis may aid in the development of new targeted therapies for angiogenic diseases. The aim of the present review was to provide a comprehensive overview of cxs and cx-mediated angiogenesis, with a focus on therapeutic implications. Contents1. Introduction 2. Methodology 3. cxs, diseases and potential therapies 4. conclusions and future directions

Opening of Cx43-formed hemichannels mediates the Ca2+ signaling associated with endothelial cell migration

“…In this context, it is important to note that treatment with Cx blocking peptides for short periods of time (< 45 min) only inhibits hemichannel activity, without affecting gap junction channels, which are blocked by longer application of these peptides (> 1 hr) [13,29,30]. In addition, although endothelial cell migration has been associated with changes in gap junction communication [10,24,31], we found that, in mesenteric endothelial cells, the level of intercellular coupling via gap junction was similar in the migration front as compared with that observed in endothelial cells before scratching the intact monolayer (Fig. 3).…”

Identification of angiogenesis‐related subtypes, the development of a prognosis model, and features of tumor microenvironment in colon cancer

“…4 Instead of the normal blood vessels, tumor neovascularization is characterized by weak vascular wall, extensive vascular endothelial space, high vascular permeability, and structural disorder. 5 Angiogenesis-related factors are often overexpressed in tumors. 6 Neovascularization is immature and highly heterogeneous, leading to reducing immune cell infiltration and activity and increasing the probability of cancer metastasis.…”

“…7 Angiogenesis provides additional nutrient supply to tumor cells, so antiangiogenesis is a promising antitumor therapeutic method. 5 Immunotherapy is a promising antitumor strategy and has achieved promising results in many clinical studies. [8][9][10] Immune checkpoint inhibitors for PD-1, PD-L1, and CTLA-4 are used in the molecularly targeted therapy of colon cancer.…”

“…Angiogenesis is important for tumor occurrence and deterioration, and the progression is regulated by growth factors, proangiogenic cytokines, and neovascularization antagonists 4 . Instead of the normal blood vessels, tumor neovascularization is characterized by weak vascular wall, extensive vascular endothelial space, high vascular permeability, and structural disorder 5 . Angiogenesis‐related factors are often overexpressed in tumors 6 .…”

“…Neovascularization is immature and highly heterogeneous, leading to reducing immune cell infiltration and activity and increasing the probability of cancer metastasis 7 . Angiogenesis provides additional nutrient supply to tumor cells, so antiangiogenesis is a promising antitumor therapeutic method 5 …”