Interleukin-1beta-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-1beta (IL-1beta), 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-1beta in cardiac microvascular endothelial cells (CMECs) and aortic tissue. Cell cycle progression analysis using flow cytometry indicated a G0/G1 phase cell cycle arrest in IL-1beta-stimulated cells. IL-1beta significantly reduced levels of fibrillar actin in the cytoskeleton, a pre-requisite for tube formation, as indicated by phalloidin-FITC staining. Wound healing assays demonstrated IL-1beta prevents cell-to-cell contact formation. On the other hand, vascular endothelial growth factor-D (VEGF-D) initiated restoration of the cell monolayer. IL-1beta significantly inhibited in vitro tube formation as analyzed by three-dimensional collagen matrix assay. Aortic ring assay demonstrated that IL-1beta 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-1beta impedes the process of angiogenesis in myocardial endothelial cells.
Mountain
Deidra J H
DJ
Department of Physiology, James H. Quillen College of Medicine, James H. Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, TN 37614, United States.
Singh
Mahipal
M
Singh
Krishna
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects
D000199:Actins; D053583:Interleukin-1beta