title: Endothelial release of tissue-type plasminogen activator and ischemia-induced vasodilatation are linked in patients with coronary heart disease.
abstract: Dysfunction in the vascular endothelium disturbs blood flow and predisposes individuals to atherosclerosis. Deteriorated fibrinolysis may further enhance the risk for atherothrombosis. We investigated 14 healthy volunteers and 24 patients with coronary heart disease. Endothelium-dependent (acetylcholine- and ischemia-induced) and endothelium-independent (nitroprusside-induced) vasodilatation in the forearm vasculature were studied using strain-gauge plethysmography, and the fibrinolytic system measured as the response of tissue plasminogen activator (t-PA) to provocation testing (20 min venous occlusion; VOT). When acetylcholine-induced vasodilatation was measured, endothelium-dependent vasodilatation differed between groups: those with coronary heart disease had a median value of 8.5 ml/min per 100 g tissue (25th to 75th percentile 4.8-10.3), compared with 11.6 ml/min per 100 g tissue (7.3-15.5) among healthy volunteers (P = 0.03). However, ischemia-induced vasodilatation showed no difference between the groups [26.8 (22.7-35.0) versus 29.1 (25.6-30.7) ml/min per 100 g tissue, respectively, NS]. Levels of t-PA after VOT also showed no difference between the groups [21.5 (16.5-31.9) versus 20.4 (11.8-31.5) ng/ml, respectively, NS]. Results of ischemia tests and levels of t-PA after VOT correlated only in patients with coronary heart disease (r = 0.5, P = 0.015), and not in healthy volunteers. We observed a positive correlation between endothelium-dependent vasodilatation function and endothelial release of t-PA. This indicates that the same mechanism that results in defective ischemia-induced endothelial relaxation in patients with coronary heart disease may also result in suppressed fibrinolytic capacity, thus making such patients more prone to atherothrombosis.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Finland. juha.sinisalo@huch.fi
authors.forename: J
authors.initials: J
authors.lastname: Sinisalo
authors.forename: M
authors.initials: M
authors.lastname: Syrjälä
authors.forename: K J
authors.initials: KJ
authors.lastname: Mattila
authors.forename: T
authors.initials: T
authors.lastname: Kerman
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
mesh_terms: D000328:Adult; D003327:Coronary Disease / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D010959:Tissue Plasminogen Activator