Coronary thrombosis is the most serious cardiovascular emergency, commonly seen in Acute Coronary Syndrome (ACS). It is a group of severe coronary artery disease types with coronary atherosclerotic thrombosis. It includes unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), ST-segment elevation myocardial infarction (STEMI), and sudden death (SD). Although clinical efficacy has been achieved with intensive antiplatelet and anticoagulation therapy and pro-fibrinolytic (thrombolytic) therapy, thrombosis (acute myocardial infarction) still occurs in 40-90% of patients on medication, and some patients develop acute, subacute and late thrombosis in stent and non-stent after treatment with PCI [1]. The current routine coagulation tests for monitoring and evaluating the propensity for thrombosis often do not provide valuable information.
Clinical and basic studies to date suggest that coronary thrombosis is primarily due to the coagulation waterfall response initiated after coronary artery injury [2]. The processes related to platelets, coagulation and fibrinolysis are well understood and allow for in vitro tests for diagnostic evaluation and to guide clinical antiplatelet, anticoagulation and thrombolytic therapy. However, there is no conclusive evidence on the initiating link of coronary thrombosis – the vessel wall – and there is no conclusive clinical examination or effective treatment [3].
The role of Tissue Factor (TF) in arterial thrombosis has long been noted by basic researchers. Recent studies have suggested that Tissue Factor is released following injury and stimulation of the vessel wall and initiates the coagulation waterfall response [4]. It is the most critical initial factor in initiating coagulation. The role of tissue factor in coronary thrombosis is reviewed as follows, with the aim of further research for better clinical prediction of thrombosis screening methods to guide clinical practice.
1.Definition and source of tissue factor (TF)
1.1, Tissue factor is a major regulator of the normal hemostasis and thrombosis process [5], it is a transmembrane glycoprotein that activates factor VII to form TF and factor VII complexes and activate cofactors throughout the coagulation waterfall [6].TF is encoded by a 12.4 kb gene located on chromosome 1 at locus 1p22-23, which consists of six exons and five introns [7].
1.2, Tissue factor is expressed on cells of the vessel wall that are not in direct contact with blood [8], and injury and various stimuli can contribute to the expression of monocytes, smooth muscle cells, outer stromal cells, endothelial cells, platelets and cell-free plaque TF [9].TF is also present in whole blood and plasma of healthy adults at concentrations of about 149-172 pg/ml [10], but the concentrations in blood are much lower than in the vessel wall [11], and TF is present in higher concentrations in the brain, lung and placenta; moderately in the heart, kidney, intestine and uterus, and less in the spleen, thymus, skeletal muscle and liver [12].
2. tissue factor is a key factor in the initiation of coronary thrombosis
Abnormal TF expression from macrophage-derived TF within coronary plaques triggers intravascular coagulation waterfalls and promotes thrombus formation [2,4]. When the coronary artery wall is damaged or stimulated, TF is released, which binds to factor VII (FⅦ) to form a complex and induces inactive FⅦ to become active FⅦa. In addition to this, TF increases the protein hydrolase and amylase activities of FVIIa and TF/FVIIa, converting factor X (FX) to FXa, which in turn changes fibrinogen to fibrin, completing the The TF/FVIIa complex also converts factor IX (FⅨ) to FⅨa and in turn acts as a cofactor for factor VIIIa (FVIIIa) to activate FX, thus participating in the endogenous coagulation pathway [13].
3, High tissue factor expression in unstable plaques of ACS is associated with the risk and prognosis of coronary artery disease
3.1, Relationship between TF expression and the nature of coronary artery lesions
TF expression did not correlate significantly with the degree of stenosis on coronary angiography [14], and some stable lesions with severe stenosis did not have a tendency for increased TF release and increased thrombotic incidence. The rupture of high-risk vulnerable plaques releases tissue factor (TF), which causes ACS thrombosis [15-16]. There are many studies on the occurrence of in-stent thrombosis after interventional balloon dilatation with stent placement showing a significant increase in circulating TF and TF-ag after PCI, causing in-stent thrombosis [17]. Some studies have suggested that overexpression of MMP-9 promotes TF release after PCI [18]
3.2, Certain stimuli act on the coronary vessel wall to increase TF release and induce thrombus formation.
Some studies suggest that neodisc g, nicotine and cotinine can promote TF release, which has a consequent role in promoting coronary thrombosis [19-20].
3.3, Drug eluting on the stent
Sirolimus increases smooth muscle TF levels, but does not affect TF activity [21]; rapamycin slightly inhibits TFPI activity, which, combined with its restenosis-preventing effect, makes rapamycin beneficial in clinical treatment [22]. It has been suggested that paclitaxel stent enhances TF expression [23].
3.4, Certain genetic alterations affect TF expression
Some authors have confirmed through their studies that Grp78 can negatively regulate TF expression [24]. And certain gene mutation types are highly expressed TF [25].
4. Tissue factor is an important target for future coronary thrombosis control
Researchers have started to actively search for substances that can inhibit TF expression and prevent coronary thrombosis by down-regulating TF expression. It has been found that IL10 can down-regulate TF expression and thus inhibit thrombosis [26]. TFPI can bind to TF and inhibit its expression [27]. p-amidinophenylurea 18, the pyrimidinones PHA-927, pyridinone 37, etc. also have the effect of inhibiting TF/FVIIa activity [28 ]. Statins can reduce TF activity [21,29]. Conventional antiplatelet agents, such as aspirin and poliovirus, can inhibit TF expression [30].
5, Outlook
The role of tissue factor in coronary thrombosis has been clarified, and in the future, we will further investigate the factors and pathways affecting high tissue factor expression, study its relationship with the risk of coronary thrombosis, and then develop appropriate tests for clinical coronary thrombosis prediction, as well as conduct research on TF and TF/FVIIa inhibitory drugs to improve the therapeutic effect.