Adrenomedullin alleviates not only neointimal formation but also perivascular hyperplasia following arterial injury in rats.
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.
Tsuruda
Toshihiro
T
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Japan. ttsuruda@med.miyazaki-u.ac.jp
Kato
Johji
J
Matsui
Eizaburo
E
Hatakeyama
Kinta
K
Masuyama
Hiroyuki
H
Imamura
Takuroh
T
Kitamura
Kazuo
K
Asada
Yujiro
Y
Eto
Tanenao
T
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
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin