Interleukin-1β-mediated inhibition of the processes of angiogenesis in cardiac microvascular endothelial cells

Angiogenesis, the formation of new capillaries from preexisting vessels, plays an essential role in revascularization of the myocardium following myocardial infarction (MI). Interleukin-1 beta (IL-1 beta), a proinflammatory cytokine increased in the heart following MI, is shown to be essential for angiogenesis in the invasiveness of tumor cells, the progression of arthritic conditions and endometriosis, and the promotion of wound healing. Here we studied the steps of angiogenesis in response to IL-1 beta in cardiac microvascular endothelial cells (CMECs) and aortic tissue. Cell cycle progression analysis using flow cytometry indicated a G(0)/G(1), phase cell cycle arrest in IL-1 beta-stimulated cells. IL-1 beta significantly reduced levels of fibrillar actin in the cytoskeleton, a pre-requisite for tubeformation, as indicated by phalloidin-FITC staining. Wound healing assays demonstrated IL-1 beta prevents cell-to-cell contact formation. On the other hand, vascular endothelial growth factor-D (VEGF-D) initiated restoration of the cell monolayer. IL-1 beta significantly inhibited in vitro tube formation as analyzed by three-dimensional collagen matrix assay. Aortic ring assay demonstrated that IL-1 beta inhibits basal and VEGF-D-stimulated microvessel sprouting from aortic rings. The data presented here are novel and of significant interest, providing evidence that IL-1 beta impedes the process of angiogenesis in myocardial endothelial cells. Published by Elsevier Inc.