title: Adrenomedullin alleviates not only neointimal formation but also perivascular hyperplasia following arterial injury in rats.
abstract: Producing components of the extracellular matrix, the vascular adventitia has been recognized as an important modulator of the vascular remodeling process, which determines the vessel architecture. In this study, we examined the effect of the vasodilator peptide adrenomedullin on vascular remodeling induced by balloon injury of rat carotid arteries. Endothelial denudation with wall stretch by ballooning not only induced neointimal formation accompanied with a reduced ratio of the lumen to vessel area, but also increased the fibroblast number and collagen deposition in the adventitial layer. When compared with the saline infusion, intravenous adrenomedullin infusion at 200 ng/h for 14 days suppressed the neointimal formation (-33%, P=0.033), reversing the ratio of lumen to vessel ratio (P=0.030), without affecting systolic blood pressure. Moreover, the adrenomedullin infusion decreased the number of adventitial fibroblasts (-41%, P<0.001) and the collagen deposition (-36%, P=0.006) in the adventitial layer of the injured artery. In conclusion, the intravenous adrenomedullin infusion effectively attenuates vascular remodeling following the arterial injury via suppression of hyperplasia in the intima and adventitia, suggesting a potential of adrenomedullin as a therapeutic tool against vascular remodeling.
authors.affiliation: First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Japan. ttsuruda@med.miyazaki-u.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tsuruda
authors.forename: Johji
authors.initials: J
authors.lastname: Kato
authors.forename: Eizaburo
authors.initials: E
authors.lastname: Matsui
authors.forename: Kinta
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Masuyama
authors.forename: Takuroh
authors.initials: T
authors.lastname: Imamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
authors.forename: Tanenao
authors.initials: T
authors.lastname: Eto
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000150:complications*; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D008297:Male; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin