Marked increase in the histamine content of neointima after stent implantation of pig coronary artery and growth-promoting effects of histamine in cultured smooth muscle cells.
After coronary stent implantation, the unfavorable in-stent restenosis often occurs by the formation of neointima due to the proliferation of smooth muscle cells. Platelet-derived growth factor (PDGF) and other peptide growth factors contribute to this process, but little is known about the role of non-peptide factors in this process. In the present study, the role of histamine, a non-peptide factor, in the formation of neointima was investigated using a pig coronary model of in-stent restenosis and a culture system of coronary smooth muscle cells. A Palmaz-Schatz stent was implanted in the left anterior descending coronary artery of male pigs. At 1, 2 and 4 weeks after stenting, the histamine content of neointima was determined to be 326 +/- 82, 1427 +/- 280 and 440 +/- 69 pmol/mg protein, respectively, by HPLC fluorometry. In contrast, the histamine content of arterial media from the untreated control arteries was only 15.3 +/- 1.6 pmol/mg protein. These results demonstrate that the histamine content of neointima is about 20 to 90-fold that of the normal media. In vitro, histamine by itself did not stimulate the proliferation of cultured smooth muscle cells, but potentiated the PDGF-stimulated proliferation of the cultured cells via a mechanism independent of H1 and H2 histamine receptors. Thus, histamine may be an important non-peptide factor in the pathogenesis of in-stent restenosis.
Fang
Yang-Il
YI
Department of Pharmacology, Showa University, School of Pharmaceutical Sciences, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. fang@pharm.showa-u.ac.jp
Namiki
Hisataka
H
Tsunoda
Eriko
E
Shioda
Seiji
S
Shibata
Masayuki
M
Nakatani
Masaki
M
Katagiri
Takashi
T
Takeyama
Youichi
Y
Ohata
Hisayuki
H
Honda
Kazuo
K
Momose
Kazutaka
K
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000601:surgery; D006632:Histamine / Q000737:chemistry / Q000378:metabolism*; D006633:Histamine Antagonists / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000737:chemistry* / Q000166:cytology
D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine