Abstract： Background The association between vulnerability of plaque assessed with intravascular ultrasound (IVUS) and plasma levels of fibrinolytic biomarkers was determined in patients with acute coronary syndrome(ACS).However,few data are available on the relationship between the levels of tissue type plasminogen activator(t-PA)and virtual histological intravascular ultrasound(VH-IVUS)signs of plaque instability.Methods Eighty-nine patients with ACS were enrolled in the study.Blood was collected to measure t-PA levels by liquid phase bead flow cytometry.Eighty-nine nonbifurcate lesions(identified by coronary angiography and ECG)were investigated using IVUS before catheterization.IVUS radiofrequency data Obtained with a 20 MHz catheter were analyzed with IVUS virtual histological software.The areas of plaque and media were calculated and lesions were classified into two groups:VH-IVUS derived thin cap fibroatheroma(VH-TCFA)and non-VH-TCFA plaque.Results Plasma t-PA levelin the patients with TCFA was significantly lower than that with non-TCFA ((1489±715) pg/ml vs(2163±1004)pg/ml).Decreased plasma levels of t-PA were associated with plaque vulnerability.Plasma levels of t-PA correlated negatively with plaque plus media and necrotic core in plaque in patients with ACS.Conclusions t-PA is an independent risk factor and a powerful predictor of vulnerable plaques.Decreased levels of t-PA may reflect instability of atherosclerotic plaques and might therefore serve as noninvasive determinants of those at high risk for consequent adverse events.