Role of histamine produced by bone marrow-derived vascular cells in pathogenesis of atherosclerosis.
To clarify the role of histamine-producing cells and its origin in atherosclerosis, we investigated histidine decarboxylase (HDC; histamine-producing enzyme) expression in murine arteries with vascular injuries after the animal had received transplanted bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. The neointima in the ligated carotid arteries contained BM-derived HDC+ cells that expressed macrophage (Mac-3) or smooth muscle cell antigen (alpha-SMA). In contrast, the HDC+ BM-derived cells, which were positive for Mac-3, were mainly located in the adventitia in the cuff replacement model. In apolipoprotein E-knockout mice on a high cholesterol diet, BM-derived cells expressing Mac-3 in the atheromatous plaques were also positive for HDC. In comparison with wild-type mice, HDC-/- mice showed reduced neointimal thickening and a decreased intima-to-media ratio after ligation and cuff replacement. These results indicate that histamine produced from BM-derived progenitor cells, which could transdifferentiate into SMC- or macrophage-like cells, are important for the formation of neointima and atheromatous plaques.
Sasaguri
Yasuyuki
Y
Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental of Health, Kitakyushu, Japan. yasu-s@med.uoeh-u.ac.jp
Wang
Ke-Yong
KY
Tanimoto
Akihide
A
Tsutsui
Masato
M
Ueno
Hikaru
H
Murata
Yoshitaka
Y
Kohno
Yukari
Y
Yamada
Sohsuke
S
Ohtsu
Hiroshi
H
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001158:Arteries / Q000166:cytology*; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000201:enzymology*; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000235:genetics; D006632:Histamine / Q000096:biosynthesis / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006949:Hyperlipidemias / Q000150:complications; D008026:Ligation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000201:enzymology*; D017539:Tunica Intima / Q000473:pathology
D001057:Apolipoproteins E; D049452:Green Fluorescent Proteins; D006632:Histamine; D006640:Histidine Decarboxylase