Background: Tissue factor (TF) is a key mediator of atherosclerotic plaque thrombogenicity and may be regulated by plaque TF pathway inhibitor (TFPI). High atherogenic lipoproteins are a well-known arterial risk factor, but their effects on the TF/TFPI balance in atherosclerotic plaques, as well as those of widely used lipid-lowering agents such as statins, are incompletely understood.
Objectives: We analyzed the TF/TFPI balance in carotid plaques from 86 patients, according to the presence of dyslipidemia and statin therapy.
Results: In patients with untreated dyslipidemia (ApoB/ApoA1 ratio >0.7) (D+) (n=44), TF antigen (TF) tended to be higher than in those without dyslipidemia (D-) (n=16). In patients with statins (S+) (n=26), TF was lower than in D+ (p=0.02) and similar to that of D- patients. TFPI antigen was higher in D- than in D+ and S+ patients (p<or=0.02). As a result, the TF/TFPI (mol/mol) ratio was higher in D+ than in D- or S+ patients (p<or=0.005). TF activity correlated to TF/TFPI ratio (p<0.0001), and was higher in the D+ than in the D- and in the S+ patients (p=0.02). Among analyzed clinical risk factors and biological parameters, including CRP, dyslipidemia was the only independent predictor for low plaque TFPI and high TF/TFPI ratio. Histochemistry showed that TF and TFPI were mainly expressed in macrophage-rich regions surrounding the lipid-rich core in the three groups.
Conclusions: These results indicate that dyslipidemia is associated with a shift of the TF/TFPI balance and of TF activity toward higher plaque thrombotic potential. Statins correct this equilibrium mainly by decreasing plaque TF together with blood atherogenic lipoproteins.