Abstract
In porcine heart, embolization of small coronary arteries with microspheres in 25 µm in diameter induces collateral capillary vessel growth by angiogenesis in and around focal necrosis. By histological analysis the inflammatory infiltrates in this porcine tissue were characterized by numerous monocytes/macrophages and fibroblasts as well as neutrophils and numerous capillaries, some in mitosis. The aim of the present study, therefore, was to clarify the role of monocytes/macrophages and fibroblasts in angiogenesis and in repair in ischemic porcine myocardium. Using a human acidic fibroblast growth factor (aFGF) cDNA probe for in situ hybridisation labeling for aFGF mRNA was seen in monocytes and macrophages only, beginning at day 1, with a maximum at 3 and 7 days, and minimal labeling at 4 weeks. We have also shown, with a specific antibody and fluorescence microscopy, that tumur necrosis factor alpha (TNFα) follows the same time sequence and that it is produced by monocytes/ macrophages. The number of capillaries in infiltrates at 3 and 7 days as revealed by the lectin Dolichus Biflorus Agglutinin was high and declined at 4 weeks. In situ hybridisation using a rat cDNA probe for fibronectin showed the increased production of fibronectin mRNA in fibroblasts. To describe the expression of fibronectin and the collagens I, III, VI immunohistochemistry was used. A comparison showed that fibroblasts produced fibronectin mRNA starting at day 3, but the protein was only maximally expressed at day 7 and 4 weeks. Collagen I, III, VI expression was highest at 1-4 weeks. Conclusion: monocytes and macrophages produce the growth factors aFGF and TNFa which seem to be important for angiogenesis in the ischemic myocardium. Fibroblasts, while they produce fibronectin and collagen, exert their major function in repair and scar formation, but may take also part in angiogenesis. (Mol Cell Biochem 147: 13–19, 1995)
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Cotran R, Kumar V, Robbins S: Healing and Repair, 1989
Schaper J, Weihrauch D: Collateral vessel development in the porcine and canine heart. In: W. Schaper, J. Schaper (ed.). Collateral Circulation — Heart, Brain, Kidney, Limbs. Kluwer Academic Publishers, Boston/Dordrecht/London, 1993, pp 65–102
Zimmermann R, Schaper J, Münkel B, Mohri M, Schaper W: In situ hybridization studies of acidic fibroblast growth factor (aFGF) in ischemic porcine myocardium. J Mol Cell Cardiol 25 (Suppl I): IX P 3 (abstr), 1993
Chilian WM, Mass Hi, Williams SE: Microvascular occlusions promote coronary collateral growth. Am J Physiol 258: H 1103—H 1111, 1990
Nathan C: Secretory products of macrophages. J Clin Invest 79: 319–322, 1987
Schaper J, König R, Franz D, Schaper W: The endothelial surface of growing coronary collateral arteries. Intimai margination and diapedesis of monocytes. A combined SEM and TEM study. Virch Arch A (Pathol Anat) 370: 193–205, 1976
Polverini P, Cotran R, Gimbrone M: Activated macrophages induce vascular proliferation. Nature 269: 804–806, 1977
Knighton D, Hunt T, Scheuenthul H: Oxygen tension regulates the expression of angiogenesis factors by macrophages. Science 221: 1283–1258, 1983
Klagsbrun M, D’Amore PA: Regulators of angiogenesis. Annu Rev Physiol 53: 217–239, 1991
Folkman J, Klagsbrun M:Angiogenic factors. Sci 235: 442–447, 1987
Schaper W: New paradigms for collateral vessel growth. Basic Res Cardiol 88: 193–198, 1993
Leibovich S, Polverini P, Shepard H: Macrophage induced angiogenesis is mediated by tumor necrosis factor alpha. Nature 329: 630–632, 1987
Frater-Schröder M, Risau W, Hallmann R: Tumor necrosis type alpha, a potent inhibitor of endothelial cellgrowth in vitro, is angiogenic in vivo. Proc Natl Acad Sci USA 84: 5277–5281, 1987
Rosenbaum J, Howes E, Rubin R: Ocular inflammatory effects of intravitreally-injected tumor necrosis factor. Am J Pathol 133: 47–53, 1988
Fahey T, Sherry B, Tracey K: Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1. Cytokine 2: 92–99, 1990
Castagnoli C, Stella M, Berthod: TNF production and hypertrophie scarring. Cell Immunol 147: 51–63, 1993
Hynes RO, Yamada KM: Fibronectins: Multifunctional modular glycoproteins. J Cell Biol 95: 369–377, 1982
Vlodaysky I, Folkman J, Sullivan R: Endothelial cell-derived basic fibroblast growth factor: Synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci USA 84: 2292–2296, 1987
Ingber D, Folkman J: Inhibition of angiogenesis through modulation of collagen metabolism. Lab Invest 59: 44–51, 1988
Nicosia RF, Belser P, Bonnano E: Regulation of angiogenesis in vitro by collagen metabolism. In Vitro Cell Dev Biol 27A: 961–966, 1991
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Weihrauch, D., Arras, M., Zimmermann, R., Schaper, J. (1995). Importance of monocytes/macrophages and fibroblasts for healing of micronecroses in porcine myocardium. In: Slezák, J., Ziegelhöffer, A. (eds) Cellular Interactions in Cardiac Pathophysiology. Developments in Molecular and Cellular Biochemistry, vol 14. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2005-4_2
Download citation
DOI: https://doi.org/10.1007/978-1-4615-2005-4_2
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5828-2
Online ISBN: 978-1-4615-2005-4
eBook Packages: Springer Book Archive