Magomed Khaidakov1, Sona Mitra, Jawahar L Mehta. 1. University of Arkansas for Medical Sciences, Department of Internal Medicine, and the Veterans Affairs Medical Center, Little Rock, Arkansas 72212, USA. mkhaidakov@uams.edu
Abstract
BACKGROUND: The development of neovasculature correlates with plaque instability and rupture as well as tumor growth and aggressiveness. In recent years, aspirin has emerged as a powerful modality in prophylaxis of cardiovascular events, which may be linked to its inhibitory effects on angiogenesis. METHODS AND RESULTS: We studied the role of endothelial adherens junctions in angiogenesis and the modulation of adherens junctions by acetylsalicylic acid (ASA) and salicylic acid as mechanisms of the angiostatic potential of these agents. Exposure of human umbilical cord endothelial cells (HUVECs) to vascular endothelial growth factor (VEGF) significantly enhanced tube formation. The disruption of adherens junctions as well as phosphorylation and cytoplasmic translocation of VE-cadherin and p120 catenin were early consequences of VEGF addition to the medium bathing the HUVECs. Pretreatment with ASA and salicylic acid prevented changes in adherence junction proteins and inhibited VEGF-induced tube formation by HUVECs in a dose-dependent manner. CONCLUSION: Angiogenesis is associated with significant alterations in adherens junctions. Both ASA and salicylic acid reduce angiogenesis by modulating adherens junctions.
BACKGROUND: The development of neovasculature correlates with plaque instability and rupture as well as tumor growth and aggressiveness. In recent years, aspirin has emerged as a powerful modality in prophylaxis of cardiovascular events, which may be linked to its inhibitory effects on angiogenesis. METHODS AND RESULTS: We studied the role of endothelial adherens junctions in angiogenesis and the modulation of adherens junctions by acetylsalicylic acid (ASA) and salicylic acid as mechanisms of the angiostatic potential of these agents. Exposure of human umbilical cord endothelial cells (HUVECs) to vascular endothelial growth factor (VEGF) significantly enhanced tube formation. The disruption of adherens junctions as well as phosphorylation and cytoplasmic translocation of VE-cadherin and p120 catenin were early consequences of VEGF addition to the medium bathing the HUVECs. Pretreatment with ASA and salicylic acid prevented changes in adherence junction proteins and inhibited VEGF-induced tube formation by HUVECs in a dose-dependent manner. CONCLUSION: Angiogenesis is associated with significant alterations in adherens junctions. Both ASA and salicylic acid reduce angiogenesis by modulating adherens junctions.