title: Maladaptive arterial remodeling with systemic hypertension associated with increased concentrations in blood of plasminogen activator inhibitor type-1 (PAI-1).
abstract: Increased carotid artery intima-media thickness (IMT), but not necessarily peripheral vessel IMT, accompanies atherosclerosis. We hypothesized that IMT in a peripheral, muscular artery known to be resistant to atherosclerotic changes would increase with hypertension, thereby limiting increases in wall stress and potentially preserving endothelial cell function reflected by flow-mediated dilation (FMD). Plasminogen activator inhibitor type-1 (PAI-1) can inhibit vascular smooth muscle cell migration contributing to increased IMT. Thus, increased PAI-1 may attenuate the mural adaptive response. A high-resolution scanner designed to delineate brachial artery FMD and IMT was used in studies of previously untreated patients with essential hypertension (n = 18) and age- and gender-matched normotensive subjects (n = 15). Brachial IMT was increased with hypertension (0.36 +/- 0.07 vs 0.27 +/- 0.03 mm in controls, p <0.01), and FMD was lower (3.6 +/- 1.5% vs 7.8 +/- 3.6, p <0.01). PAI-1 antigen in blood was increased (40.5 +/- 31.8 vs 26.3 +/- 11.6 ng/ml, p <0.05). IMT and FMD correlated positively (r = 0.63, p <0.05) in hypertensive patients. FMD correlated inversely with wall stress (r = -0.57, p <0.05). IMT correlated inversely with PAI-1 (r = -0.61, p <0.05). These observations support the hypothesis that increased PAI-1 attenuated increases in neointimal vascular smooth muscle cell cellularity. Thus, increased PAI-1 may attenuate a mural, adaptive response to hypertension associated with preservation of endothelial cell function.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine and College of Medical Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Furumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishihara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.forename: Kaoru
authors.initials: K
authors.lastname: Komuro
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Goto
authors.forename: Hisao
authors.initials: H
authors.lastname: Onozuka
authors.forename: Taisei
authors.initials: T
authors.lastname: Mikami
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.forename: Burton E
authors.initials: BE
authors.lastname: Sobel
mesh_terms: D002339:Carotid Arteries / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000502:physiology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: D017395:Plasminogen Activator Inhibitor 1