title: 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.
abstract: 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.
authors.affiliation: 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
authors.forename: Yang-Il
authors.initials: YI
authors.lastname: Fang
authors.forename: Hisataka
authors.initials: H
authors.lastname: Namiki
authors.forename: Eriko
authors.initials: E
authors.lastname: Tsunoda
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibata
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Katagiri
authors.forename: Youichi
authors.initials: Y
authors.lastname: Takeyama
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Ohata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Honda
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Momose
mesh_terms: 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
chemical_list: D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine