Impact of angiogenesis inhibitors on inflammatory activation in human vascular endothelial cells
Abstract
Background: The initiation and progression of inflammation can elevate the secretion of angiogenesis activators, which bind to receptors on endothelial surfaces, thereby stimulating cell proliferation and enhancing migration which has emerged as a significant risk factor for atherosclerosis.
Material and methods: To investigate the effectiveness of angiogenesis inhibitors on changes in blood vessels, the study utilized the anti-angiogenic drugs bevacizumab, pazopanib, and KRN-633. In the study, the vascular model comprised primary human coronary artery endothelial cells (pHCAECs). Moreover, the inflammatory response was induced by the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α).
Results: The compounds’ effect on pHCAECs induced structural changes within the actin cytoskeleton, demonstrating the presence of entosis and apoptotic vesicle-like structures. Additionally, inflammation in the pHCAEC line exacerbated the effects of the compounds used in the study, leading to heightened disintegration of cellular cytoskeletons. Conversely, pazopanib in combination with TNF-α induced the formation of vesicular structures along the course of F-actin retraction fibres in migrating pHCAECs. Furthermore, KRN-633 combined with TNF-α resulted in the translocation of VE-cadherin to the cell nucleus in these cells.
Conclusions: It is noteworthy that current treatments for cardiovascular diseases are not entirely effective. The utilization of functional pharmacological compounds such as angiogenesis inhibitors may provide an effective approach to treating disorders and regulating cardiovascular function.
Keywords: endotheliuminflammationangiogenesisTNF-αbevacizumabpazopanibKRN-633
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