Increased levels of tPA antigen and tPA/PAI-1 complex in myotonic dystrophy.

摘要

OBJECTIVE: To assess the fibrinolytic system in myotonic dystrophy (DM1), a disease connected to features of the metabolic syndrome, including a prominent insulin resistance, increased body fat mass, and hypertriglyceridaemia. We hypothesized that abnormalities in the fibrinolytic system are linked to metabolic dysfunction in DM1. DESIGN: Circulating morning levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) antigens, tPA/PAI-1 complex, lipids and insulin were determined. Genetic analyses, including calculation of allele size, were performed in all patients. Body fat mass was estimated with bioelectrical impedance analysis. SETTING: Out-patient clinic in collaboration with Umea University Hospital. SUBJECTS: A total of 42 otherwise healthy patients with DM1 (22 men, 20 women; median age 41.5 years) and 50 controls (27 men, 23 women; median age 42.0 years). MAIN OUTCOME MEASURES: The tPA and PAI-1 antigens, tPA/PAI-1 complex, blood lipids and body fat mass. RESULTS: The tPA antigen and tPA/PAI-1 complex levels were significantly increased in DM1 patients (P < 0.001 and P < 0.05, respectively) whilst levels of PAI-1 did not differ from controls. Triglyceride levels were increased (P < 0.001) whereas HDL cholesterol levels were lower in DM1 patients (P < 0.05). Body fat mass was increased in DM1 patients (P < 0.001). CONCLUSIONS: The fibrinolytic system is disturbed in DM1 patients, with increased levels of tPA and tPA/PAI-1 complex but paradoxically unaltered levels of PAI-1, in spite of a severely increased body fat mass. This may imply an abnormal function of adipose tissue in DM1, and calls for further studies of the fibrinolytic system in this disease.bstra