Endocannabinoids and related compounds as modulators of angiogenesis: Concepts and clinical significance

• Published in: Cell biochemistry and function Vol. 40; no. 8; pp. 826 - 837
• Main Authors: Afshar, Shima, Abbasinazari, Mohammad, Amin, Gholamreza, Farrokhian, Amir, Sistanizad, Mohammad, Afshar, Fariba, Khalili, Shayesteh
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-12-2022
• Subjects: Angiogenesis; Antiangiogenic agents; Antiangiogenics; Cancer; Cannabinoids; cannabinoid‐like molecules; Capillaries; Cell differentiation; Clinical Relevance; Clinical significance; Diabetes mellitus; Diabetic retinopathy; Dispersal; Embryos; Endocannabinoid system; endocannabinoidome; Endocannabinoids; Endothelial Cells; Enzymes; Modulators; Molecular modelling; Occlusion; Retinopathy; Reviews; Tumorigenesis; Vascular endothelial growth factor; Vascular system; Wound Healing; endocannabinoidome; cancer; endocannabinoids; cannabinoid-like molecules; angiogenesis
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.3754

Vasculogenesis (the process of differentiation of angioblasts toward endothelial cells and de novo formation of crude vascular networks) and angiogenesis (the process of harmonized sprouting and dispersal of new capillaries from previously existing ones) are two fundamentally complementary processes, obligatory for maintaining physiological functioning of vascular system. In clinical practice, however, the later one is of more importance as it guarantees correct embryonic nourishment, accelerates wound healing processes, prevents uncontrolled cell growth and tumorigenesis, contributes in supplying nutritional demand following occlusion of coronary vessels and is in direct relation with development of diabetic retinopathy. Hence, discovery of novel molecules capable of modulating angiogenic events are of great clinical importance. Recent studies have demonstrated multiple angio‐regulatory activities for endocannabinoid system modulators and endocannabinoid‐like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them.
Significance statement
Regardless of the fact that antiangiogenic therapies, especially those targeting VEGF molecule and their associated pathways, may be of great potential in treatment of cancer, application of currently existing antiangiogenic agents in micrometastatic cases was together with poor clinical outcome and no meaningful enhancement in disease‐free or recurrence‐free survival. This is strongly suggestive of the ineffectiveness of the recently established approaches in suppressing cancer angiogenesis. And necessity for discovery of other more potent and effective solutions for management of angiogenic events in cancer. Recent studies have demonstrated multiple angio‐regulatory activities for endocannabinoid system modulators and endocannabinoid‐like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them.