Pathophysiological role of blood-borne tissue factor: should the old paradigm be revisited?

Abstract

The term "vulnerable plaque" identifies atherosclerotic lesions prone to rupture. Plaque disruption facilitates the interaction of the inner components of the lesion, tissue factor (TF) among them, with the flowing blood. This results in activation of the coagulation cascade, ultimately leading to thrombus formation, and abrupt vascular occlusion. Despite the central role of vulnerable plaques in the onset of acute coronary syndromes (ACS), there are certain conditions (e.g., eroded plaques) where a hyperactive, "vulnerable" blood, may play a predominant pathophysiological role. Recently, two distinct pools of circulating TF have been identified. One, associated with cell-derived microparticles probably originating from apoptotic cells, such as macrophages, smooth muscle cells, and endothelium. The most recent, blood-borne TF, circulates in an "inactive" form (encryption) and has to be activated (decryption) to exert its thrombogenic activity. Certain pathological conditions associated with an increased rate of thrombotic complications have been associated with high levels of circulating TF. It is thought that the blood-borne TF perpetuates the initial thrombogenic stimulus, leading to the formation of larger or more stable thrombus, and thus, more severe ACS. Thus, the concept of vulnerable blood could represent a new link between the vulnerable lesion and the high-risk patient. Therefore, the assessment of selected biomarkers associated with "vulnerable or hyperreactive blood", e.g., blood-borne tissue factor, may represent a useful tool to identify patients with a high-risk profile of developing major cardiovascular events.

A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

“…Pro-coagulant MVs constitute one of the main reservoirs of blood-borne TF, which are released from monocytes, macrophages, or endothelial cells with inducible TF expression [23] and they are therefore considered to be key determinants of the hemostasis equilibration [24]. Notably, the number of pro-coagulant MVs can significantly increase in patients suffering from sepsis as reported by us and other groups [13], [25].…”

Predictive role of circulating endothelial-derived microparticles in cardiovascular diseases

“…In summary, circulating EMP count probably reflects imbalance between pro-and antiangiopoetic activity in close relation with plaque formation and endothelial dysfunction. Supporting the theory that noninvasive biomarkers may predict plaque instability in asymptomatic patients, EMPs are considered a perspective candidate for further investigation [58]. In fact EMPs may contribute to thrombosis in animal models [59].…”

Blood-born tissue factor in cardiovascular disease: where are we now?

“…Experimental studies indicate that circulating TF may be important in sustaining atherothrombotic phenomena in addition to locally active TF present in the plaque. Blood-borne TF, released by leukocytes, is essential for thrombus propagation after its initial formation on the vascular surface [10]. Further studies suggest that platelets might also be a potential source of circulating TF.…”