Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin.

Abstract

Angiotropin is a differentiation factor for microvascular endothelial cells isolated from serum-free cultures of lectin-activated, porcine monocytes. We used an ear lobe model in rabbits, single intradermal injection of angiotropin to induce phenotypical changes of the endothelial cells in capillaries and postcapillary venules, vascular engorgement, and subsequent angiogenesis in dose-dependent manner. The vascular changes are associated with epidermal and stromal cell proliferation. Angiogenesis and tissue proliferation occur in the absence of tissue necrosis and do not lead to scar formation. Angiotropininduced angiogenesis is not inhibited by local dexamethasone although it involves a defined turnover of inflammatory cells.Proliferation is transient and regressive events follow. The overall tissue reaction resembles changes found in the undamaged skin margin of a primary healing wound during the inflammatory/proliferative phase. From these observations we conclude that angiotropin is an important secretory product of activated peripheral macrophages that triggers inflammatory and proliferative reactions in wound healing by activating microvascular endothelial cells.

Engineering of Blood Vessel Patterns by Angio-Morphogens [Angiotropins]:. Non-Mitogenic Copper-Ribonucleoprotein Cytokines [CuRNP Ribokines] with their Metalloregulated Constituents of RAGE-binding S100-EF-Hand Proteins and extracellular RNA Bioaptamers in Vascular Remodeling of Tissue and Angiogenesis in vitro

“…Basics and use have been reported [39]. Laser-Doppler-flow-velocimetry for quantitative assessment of blood perfusion was achieved by a MedPacific instrument, Seattle, WA.…”

Engineering of Capillary Patterns in Muscle by a Nonmitogenic Copper‐Ribonucleoprotein Angiomorphogen [Angiotropin CuRNP Ribokine]

“…The 99 Tc distribution appears almost as rapid and intense as in the large axial vessels of the body. Other techniques could show that dynamics of flow are a property of newly formed three‐dimensional networks of capillaries in tissue2‐4,7‐13 (e.g., by making capillary structures and functions accessible to visual inspection by microparticle distribution and to characterization by laser Doppler‐flow velocimetry).…”

“…Thus, the final “physiological” pattern formation is suggested to be functionally integrated with respect to host tissue involving other endogenous factors formed by morphogen‐activated cells 2‐4,11,13. Taken together with known properties, that is, its capacity for remodeling bioactive blood vessel patterns in tissue, for supporting tissue functions and preventing tissue necrosis,2‐13 angiotropin shows beneficial perspectives for further investigations in angiotherapy and engineering of biocompatible artificial organs. Potential applications include support of muscular and associated tissue functions, prevention of necrosis, angiotherapeutic aspects of bypass operations and restenosis following percutaneous transluminal coronary angioplasty, as well other disorders and risks subject to situations of changes in vascular patterns.…”

“…Thus, modes of application of an angiomorphogen in the form of angiotropin (AT) ribokine into muscle were investigated. Members of human and porcine AT cytokine (ribokine) family represent endogenous nonmitogenic endothelial cell‐selective and vascularizing morphogens of leukocytic origin 2‐13. They are extracellular copper‐ribonucleoprotein complexes (CuRNP) built up of copper ion, metalloregulated AT‐related protein (ARP), and of extracellular eRNA bioaptamer units (ARNA, 72‐78 nucleotides) of defined sequences.…”

Hematopoietic cytokines for cardiac repair: mobilization of bone marrow cells and beyond

“…GM-CSF-induced upregulation of adhesion molecules enhances the recruitment of circulating leukocytes, especially monocytes, to endothelial cells [32, 46]. GM-CSF also increases the number of circulating monocytes, which have been implicated both in angiogenesis and LV remodeling [61, 101, 165], and the level of circulating GM-CSF is elevated in patients with ischemic dilated cardiomyopathy [126]. Moreover, in models of hindlimb ischemia and ocular micropocket assay, mobilization of endothelial progenitor cells by GM-CSF has been shown to enhance angiogenesis [147].…”