Tissue factor (TF) is the high-affinity receptor and cofactor for factor (F)VII/VIIa. The TF-FVIIa complex is the primary initiator of blood coagulation and plays an essential role in hemostasis. TF ...is expressed on perivascular cells and epithelial cells at organ and body surfaces where it forms a hemostatic barrier. TF also provides additional hemostatic protection to vital organs, such as the brain, lung, and heart. Under pathological conditions, TF can trigger both arterial and venous thrombosis. For instance, atherosclerotic plaques contain high levels of TF on macrophage foam cells and microvesicles that drives thrombus formation after plaque rupture. In sepsis, inducible TF expression on monocytes leads to disseminated intravascular coagulation. In cancer patients, tumors release TF-positive microvesicles into the circulation that may contribute to venous thrombosis. TF also has nonhemostatic roles. For instance, TF-dependent activation of the coagulation cascade generates coagulation proteases, such as FVIIa, FXa, and thrombin, which induce signaling in a variety of cells by cleavage of protease-activated receptors. This review will focus on the roles of TF in protective hemostasis and pathological thrombosis.
Atherosclerosis is a chronic inflammatory disease that is characterized by the formation of lipid rich plaques in the wall of medium to large sized arteries. Atherothrombosis represents the terminal ...manifestation of this pathology in which atherosclerotic plaque rupture or erosion triggers the formation of occlusive thrombi. Occlusion of arteries and resultant tissue ischemia in the heart and brain causes myocardial infarction and stroke, respectively. Tissue factor (TF) is the receptor for the coagulation protease factor VIIa, and formation of the TF:factor VIIa complex triggers blood coagulation. TF is expressed at high levels in atherosclerotic plaques by both macrophage-derived foam cells and vascular smooth muscle cells, as well as extracellular vesicles derived from these cells. Importantly, TF mediated activation of coagulation is critically important for arterial thrombosis in the setting of atherosclerotic disease. The major endogenous inhibitor of the TF:factor VIIa complex is TF pathway inhibitor 1 (TFPI-1), which is also present in atherosclerotic plaques. In mouse models, increased or decreased expression of TFPI-1 has been found to alter atherosclerosis. This review highlights the contribution of TF-dependent activation of coagulation to atherthrombotic disease.
•Tissue Factor (TF) is highly expressed in human atherosclerotic plaques.•TF pathway inhibitor regulates atherosclerotic plaque development.•TF driven activation of coagulation is critical for atherothrombosis.
Tissue factor (TF) is induced in a variety of cell types during viral infection, which likely contributes to disseminated intravascular coagulation and thrombosis. TF‐expressing cells also release ...TF‐positive extracellular vesicles (EVs) into the circulation that can be measured using an EVTF activity assay. This review summarizes studies that analyze TF expression, TF‐positive EVs, activation of coagulation, and thrombosis after infection with influenza A virus (IAV) and coronaviruses (CoVs), including severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), SARS‐CoV, and Middle East respiratory syndrome CoV (MERS‐CoV). The current pandemic of coronavirus disease 2019 (COVID‐19) is caused by infection with SARS‐CoV‐2. Infection of mice with IAV increased TF expression in lung epithelial cells as well as increased EVTF activity and activation of coagulation in the bronchoalveolar lavage fluid (BALF). Infection of mice with MERS‐CoV, SARS‐CoV, and SARS‐CoV‐2 also increased lung TF expression. Single‐cell RNA sequencing analysis on the BALF from severe COVID‐19 patients revealed increased TF mRNA expression in epithelial cells. TF expression was observed in peripheral blood mononuclear cells infected with SARS‐CoV. TF was also expressed by peripheral blood mononuclear cells, monocytes in platelet‐monocyte aggregates, and neutrophils isolated from COVID‐19 patients. Elevated circulating EVTF activity was observed in severe IAV and COVID‐19 patients. Importantly, EVTF activity was associated with mortality in severe IAV patients and with plasma D‐dimer, severity, thrombosis, and mortality in COVID‐19 patients. These studies strongly suggest that increased TF expression in patients infected with IAV and pathogenic CoVs contributes to thrombosis.
This paper explores how treating people respectfully affects performance and work effort based on individual differences in self-esteem. Appraisal respect encompasses admiration for skills and ...abilities, and recognition respect reflects treating people in accordance with their human rights. The findings show that extant self-esteem moderates the impact of respect on performance and work effort. A laboratory study using actors to express recognition respect shows that implicit self-esteem moderates recognition respect in a self-verifying manner: People with low implicit self-esteem perform better, whereas those with high implicit self-esteem perform worse when treated with low levels of recognition respect. In contrast, explicit self-esteem moderates appraisal respect in a self-enhancement manner. People with higher explicit self-esteem perform better when they receive low levels of appraisal respect as operationalized by performance feedback. A second study surveys working adults in order to extend the findings to work effort. This study juxtaposes the two types of self-esteem. People with congruent implicit/explicit self-esteem expend more work effort when they experience recognition respect, and those with incongruent self-esteem expend more effort when they experience appraisal respect. These findings integrate self-esteem and respect theory to explain how respectful treatment affects performance.
•How respect affects performance depends on individual self-esteem.•People aware of their own high self-esteem perform better when they receive negative feedback.•People unaware of their low self-esteem perform better with low interpersonal respect.
Cancer Therapy-Associated Thrombosis Grover, Steven P; Hisada, Yohei M; Kasthuri, Raj S ...
Arteriosclerosis, thrombosis, and vascular biology,
04/2021, Letnik:
41, Številka:
4
Journal Article
Organizational scholars have invoked the concept of respect and relegated it as a common sense, under-specified construct. This article analyzes the notion of respect by drawing on philosophy and ...defines respectful behavior as the manifestation of believing another person has value. Two types of respect are identified: appraisal respect is based on individual characteristics, and recognition respect is based on being human and having rights. In the organizational context, appraisal respect is acknowledgement of work performance and recognition respect is the quality of interpersonal treatment. This article presents a new theoretical framework that juxtaposes these two types of respect to model how they have different effects on self-esteem and therefore affect attitudes and behaviors differently. This model allows future research in the organization sciences to invoke respect more precisely, especially organizational justice and leadership research that explicitly or implicitly use concepts of respect.
The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In ...patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.
Le panel principal responsable des lignes directrices 2021 a sélectionné des éléments cliniquement pertinents et a soumis des recommandations actualisées, basées sur de nouvelles découvertes d'importance apparues depuis les lignes directrices de 2016. Ainsi, le traitement par statine reste recommandé pour les patients atteints d'athérosclérose clinique, d'anévrisme de l'aorte abdominale, pour la plupart des patients diabétiques ou atteints d'insuffisance rénale chronique, et chez ceux dont le cholestérol à lipoprotéines de basse densité est ≥ 5 mmol/l. Nous avons introduit la notion de seuils pour le traitement des lipides/lipoprotéines afin d'intensifier le traitement hypolipidémiant avec des agents non-statiniques, et nous avons identifié les patients en prévention secondaire distingués comme ayant tirer le plus grand bénéfice de l'intensification du traitement avec ces agents. Pour tous les autres patients, nous mettons l'accent sur l'appréciation du risque par le biais de l'évaluation des lipides/lipoprotéines afin d'optimiser la prise de décision clinique. Le dosage de la lipoprotéine (a) est maintenant recommandé une fois dans la vie d'un patient, dans le cadre du dépistage initial des lipides pour évaluer le risque cardiovasculaire. Pour tout patient présentant des taux de triglycérides ˃ 1,5 mmol/l, l'apolipoprotéine B ou le cholestérol lié aux lipoprotéines autres que celles de haute densité sont les indices lipidiques à privilégier pour le dépistage, plutôt que le cholestérol à lipoprotéines de basse densité. Nous proposons des recommandations actualisées concernant le rôle du score calcique des artères coronaires en tant qu'outil de décision clinique pour aider à la décision d'administrer un traitement par statine. Il existe de nouvelles recommandations concernant les soins préventifs des femmes souffrant de troubles hypertensifs de la grossesse. Le changement de comportement en matière de santé, incluant l'exercice physique régulier et une alimentation saine pour le coeur, reste la pierre angulaire de la prévention des maladies cardiovasculaires. Ces lignes directrices visent à fournir une plateforme pour une discussion constructive et une prise de décision partagée entre le patient et le prestataire de soins, afin que des décisions individuelles puissent être prises pour le dépistage, l'évaluation et le traitement des risques.
Patients with coronavirus disease 2019 (COVID-19) have a high rate of thrombosis. We hypothesized that severe acute respiratory syndrome coronavirus 2 infection leads to induction of TF (tissue ...factor) expression and increased levels of circulating TF-positive extracellular vesicles (EV) that may drive thrombosis. Approach and Results: We measured levels of plasma EV TF activity in 100 patients with COVID-19 with moderate and severe disease and 28 healthy controls. Levels of EV TF activity were significantly higher in patients with COVID-19 compared with controls. In addition, levels of EV TF activity were associated with disease severity and mortality. Finally, levels of EV TF activity correlated with several plasma markers, including D-dimer, which has been shown to be associated with thrombosis in patients with COVID-19.
Our results indicate that severe acute respiratory syndrome coronavirus 2 infection induces the release of TF-positive EVs into the circulation that are likely to contribute to thrombosis in patients with COVID-19. EV TF activity was also associated with severity and mortality.
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