Contribution of monocytes/macrophages to compensatory neovascularization: the drilling of metalloelastase-positive tunnels in ischemic myocardium.
In a transgenic model of ischemic cardiomyopathy in which monocytes are attracted to the myocardium by the targeted overexpression of monocyte chemoattractant protein-1 (MCP-1), we have observed the presence of endothelial NO synthase and platelet endothelial cell adhesion molecule-1-negative tunnels, occasionally containing blood-derived cells, that probe the cardiac tissue. Immunohistochemical data show that monocytes/macrophages (MCs/Mphs) drill tunnels using the broad-spectrum mouse macrophage metalloelastase. 5-Bromo-2'-deoxyuridine incorporation and neo-endothelial markers present in the microvasculature of MCP-1 mouse hearts suggest an active angiogenic process. Further studies will be required to establish that the MC-/Mph-drilled tunnels evolve to become capillaries, connected to the existing vessels and colonized by circulating endothelial cell progenitors. This possibility is supported by the availability of these cells, which is demonstrated by cell tagging with beta-galactosidase placed under an active endothelial Tie-2 promoter. This phenomenon might represent another mechanism, in addition to the secretion of the angiogenic factors, by which MCs/MPhs may participate in the elaboration of new blood vessels in adult tissues.
Moldovan
N I
NI
Heart and Lung Institute and the Division of Cardiology, Department of Internal Medicine, College of Medicine and Public Health, Ohio State University, Columbus, Ohio 43210, USA. moldovan-1@medctr.osu.edu
Goldschmidt-Clermont
P J
PJ
Parker-Thornburg
J
J
Shapiro
S D
SD
Kolattukudy
P E
PE
D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis*; D006321:Heart / Q000503:physiopathology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000201:enzymology / Q000502:physiology*; D017202:Myocardial Ischemia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013194:Staining and Labeling; D018800:Thy-1 Antigens / Q000032:analysis
D018932:Chemokine CCL2; D018800:Thy-1 Antigens; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D008666:Metalloendopeptidases