Key result
Active TFPI in carotid plaques is linked to ~50% lower tissue factor activity.
Why the study?
The expression of tissue factor pathway inhibitor within human atherosclerotic plaque and its role in modulating tissue factor activity were not well defined.
Observational (n=34)
Absolute Event Rate: 0.14% vs 0.28%
p-value: p=0.002
Biologically active TFPI is present in human atherosclerotic plaques and is associated with attenuated tissue factor activity, suggesting a role in modulating plaque thrombogenicity.
TFPI expression in plaques may locally inhibit thrombosis; leaves open its value as therapeutic target.
BACKGROUND: Plaque disruption and exposure of subendothelial procoagulants such as tissue factor (TF) to circulating factor VII/VIIa (FVII/VIIa) lead to intravascular thrombosis. Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of TF-induced coagulation that binds to factor Xa and the TF-FVIIa catalytic complex in a two-step process. The aim of this study was to determine the expression of TFPI within human atherosclerotic plaque and its role in modulation of TF activity. METHODS AND RESULTS: We measured the level of TFPI antigen in human carotid plaque and determined the relationship between TFPI and TF activity within plaque. Furthermore, we examined the biological activity and immunolocalization patterns of TFPI within carotid plaque. TFPI was detectable (TFPI+ group) in 22 of 34 specimens (mean+/-SEM, 404. 4+/-91.8 pg/mg) and undetectable (TFPI- group) in 12 of 34 specimens. In the TFPI- group, normalized TF activity was significantly greater than that in the TFPI+ group (0.28+/-0.04 vs 0.14+/-0.02 U/pg, P=0.002). Furthermore, neutralization of TFPI activity using a polyclonal antibody resulted in an 8-fold increase in TF activity in the TFPI+ group (P=0.001) but had no effect in the TFPI- group. Immunostaining for TFPI showed localization to endothelial cells, vascular smooth muscle cells within the fibrous cap region of the plaque, and macrophages within the shoulder region of the plaque. CONCLUSIONS: Taken together, these data suggest that biologically active TFPI is present within human atherosclerotic plaque and is associated with attenuated TF activity.
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Caplice et al. (1998) conducted an observational in Atherosclerosis (n=34). Tissue Factor Pathway Inhibitor (TFPI) presence vs. Undetectable TFPI was evaluated on Normalized TF activity (p=0.002). The presence of biologically active TFPI in human carotid atherosclerotic plaques was associated with significantly lower normalized tissue factor activity (0.14 vs 0.28 U/pg, P=0.002).
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