ABSTRACT
Progressive tumor growth is dependent on angiogenesis. The mechanisms by which endothelial cells (ECs) are incorporated to develop new blood vessels are not well understood. Recent studies reveal that the ezrin radixin moesin (ERM) family members are key regulators of cellular activities such as adhesion, morphogenetic change, and migration. We hypothesized that ezrin, one of the ERM family members, may play important roles in ECs organization during angiogenesis, and new vessels formation in preexisting tissues. To test this hypothesis, in this study, we investigated the effects of ezrin gene silencing on the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were transfected with plasmids with ezrin-targeting short hairpin RNA by using the lipofectamine-2000 system. Wound assay in vitro and three-dimensional culture were used to detect the migration and angiogenesis capacity of HUVECs. The morphological changes of transfected cells were observed by confocal and phase contrast microscopy. Our results demonstrated that the decreased expression of ezrin in HUVECs significantly induced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also reduced cell migration and angiogenesis capacity in vitro, suggesting that ezrin play an important role in the process of HUVECs migration and angiogenesis.
ABSTRACT
Progressive tumor growth is dependent on angiogenesis. The mechanisms by which endothelial cells (ECs) are incorporated to develop new blood vessels are not well understood. Recent studies reveal that the ezrin radixin moesin (ERM) family members are key regulators of cellular activities such as adhesion, morphogenetic change, and migration. We hypothesized that ezrin, one of the ERM family members, may play important roles in ECs organization during angiogenesis, and new vessels formation in preexisting tissues. To test this hypothesis, in this study, we investigated the effects of ezrin gene silencing on the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were transfected with plasmids with ezrin-targeting short hairpin RNA by using the lipofectamine-2000 system. Wound assay in vitro and three-dimensional culture were used to detect the migration and angiogenesis capacity of HUVECs. The morphological changes of transfected cells were observed by confocal and phase contrast microscopy. Our results demonstrated that the decreased expression of ezrin in HUVECs significantly induced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also reduced cell migration and angiogenesis capacity in vitro, suggesting that ezrin play an important role in the process of HUVECs migration and angiogenesis.
Subject(s)
Humans , Cell Movement , Genetics , Cytoskeletal Proteins , Genetics , Metabolism , Cytoskeleton , Metabolism , Human Umbilical Vein Endothelial Cells , Cell Biology , Metabolism , Physiology , Neovascularization, Physiologic , GeneticsABSTRACT
<p><b>BACKGROUND</b>Insulin resistance (IR) is significantly associated with coronary artery disease and cardiovascular events in patients with or without type 2 diabetes mellitus. This study aimed to evaluate the influence of IR on long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation.</p><p><b>METHODS</b>A total of 467 consecutive patients undergoing SES-based PCI were divided into IR group (n = 104) and non-IR group (n = 363). The patients were followed up for one year. The rate of major adverse cardiac events (MACEs) including death, non-fatal myocardial infarction and recurrent angina pectoris was compared by the log-rank test, and the independent risk factors were identified by the Cox regression analysis.</p><p><b>RESULTS</b>MACEs occurred more frequently, and cumulative survival rate was lower in the IR group than in the non-IR group during the follow-up (all P < 0.05). IR was an independent risk factor for the occurrence of cardiac death and non-fatal myocardial infarction (OR = 2.76, 95%CI = 1.35 - 5.47, P = 0.034). Old age, diabetes, and multi-vessel disease were determinants for recurrent angina pectoris after PCI (P < 0.05). Subgroup analysis revealed that IR (OR = 3.35, 95%CI = 1.07 - 13.59, P = 0.013) and multi-vessel disease (OR = 2.19, 95%CI = 1.01 - 5.14, P = 0.044) were independent risk predictors for recurrent angina pectoris in patients with diabetes after PCI.</p><p><b>CONCLUSIONS</b>IR is associated with reduced MACE-free survival and remains an independent predictor for recurrent angina pectoris after PCI with SES implantation.</p>