Infusion of angiotensin II increases fibrinolysis in healthy individuals but not in patients with familial combined hyperlipidemia.
Impaired fibrinolysis is related to insulin resistance, also a characteristic feature of familial combined hyperlipidemia (FCHL). The renin-angiotensin (Ang) system is upregulated with insulin resistance, and there is crosstalk between Ang II and insulin-signalling pathways. We studied the fibrinolytic effects of a 3-h systemic Ang II infusion in 16 patients with FCHL and 16 controls, and placebo infusion in eight individuals. Baseline plasminogen activator inhibitor-1 (PAI-1) activity, plasmin-antiplasmin complex, insulin resistance and C-reactive protein were higher in patients with FCHL than in controls. PAI-1 activity decreased during Ang II, similar in patients with FCHL and controls, and by placebo. Plasmin-antiplasmin complex was unaffected by Ang II in FCHL but increased in controls. Patients with FCHL show signs of insulin resistance, low-grade inflammation and impaired fibrinolysis. Ang II enhances fibrinolysis in controls but not in patients with FCHL, suggesting that patients with FCHL are not capable of increasing tissue plasminogen activator activity in response to Ang II. Ang II has no short-term effects on PAI-1 activity.
aDepartment of Internal Medicine, Ryhov County Hospital, Jönköping bDivision of Cardiovascular Medicine cDivision of Internal Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm dDepartment of Medicine, Karolinska University Hospital, Huddinge, Sweden.
Mikael
M
Ekholm
Thomas
T
Kahan
Gun
G
Jörneskog
Anders
A
Bröijersén
N Håkan
NH
Wallén
D000804:Angiotensin II / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D000804:Angiotensin II