Tissue factor pathway inhibitors as a novel approach to antithrombotic therapy

Sajadi, Saeid; Ezekowitz, Michael D.; Dhond, Abhay J.; Netrebko, Pavlo I

doi:10.1358/dnp.2003.16.6.829308

Cited by 9 publications

(14 citation statements)

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“…TF is expressed at high levels by VSMC and macrophages within atherosclerotic plaques, is upregulated by cytokines favoring thrombus formation after plaque rupture and therefore its activity is associated with an increase in CVD risk in the MetS [70]. TF activity is inhibited by various agents, including TF pathway inhibitor (TFPI), whose activity reduces thrombosis in animal models [71]. Notably, TFPI activity has been negatively correlated with parameters characteristic of the insulin resistance and the MetS as well as body mass index [72].…”

Section: Prothrombotic and Proinfammatory Status In Metsmentioning

confidence: 99%

Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome

Haidara¹,

Mikhailidis²,

Yassin³

et al. 2011

CPD

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The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field.

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Section: Prothrombotic and Proinfammatory Status In Metsmentioning

confidence: 99%

Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome

Haidara¹,

Mikhailidis²,

Yassin³

et al. 2011

CPD

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“…It controls the dynamic interaction of enzymatic Factors VII, VIII, IX and X. The vascular endothelium secretes tissue factor hormone into extravascular tissues and then insulates it from the Factor VII flowing freely in blood, so that tissue damage exposes tissue factor to blood-borne Factor VII and initiates tissue repair component activity (see "Tissue Repair Component" on page 5) [177, 184,187,[194][195][196][197].…”

Section: The Central Role Of the Vascular Endotheliummentioning

confidence: 99%

“…The vascular endothelium adjusts arterial diameter via neuromuscular control to optimize diastolic turbulent mixing, which mobilizes particulate deposits from arterial walls [233,[405][406][407]. Without adequate turbulence, deposits form on the inner walls of arteries, and this activates the tissue repair component, causing thrombin and soluble fibrin generation, inflammation, tissue factor accumulation, fibrosis, and cholesterol trapping that forms atherosclerotic plaque [197,198,210,324,[408][409][410][411][412][413][414][415][416].…”

Section: The Turbulence Mechanismmentioning

confidence: 99%

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

Coleman

2010

CHDDT

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Based on Capillary Gate Theory and Tissue Repair Theory, this paper describes the "Stress Repair Mechanism" (SRM) that maintains and repairs vertebrate tissues. It accounts for most of the mysterious manifestations of allostasis that remain unexplained by Hypothalamic-Pituitary-Axis (HPA) hormones and thereby enables the Universal Theory of Medicine predicted by Hans Selye. SRM activity explains hemodynamic physiology, capillary hemostasis, infarction, Korotkoff sounds, blood pressure, hypertension, diabetes, allostasis, allostatic load, anesthesia, analgesia, atherosclerosis, apoptosis, malignancy, eclampsia, sepsis, Multi-System Organ Failure (MSOF), the surgical stress syndrome, the fight or flight response, and numerous other manifestations of physiology and pathology. SRM function comprises the autonomic nervous system, the vascular endothelium, and the dynamic enzymatic interaction of blood-borne hepatic Factors VII, VIIIC, IX and X that produces thrombin, soluble fibrin and insoluble fibrin, whose combined effects account for all SRM manifestations. The vascular endothelium is a diaphanous neuroendocrine organ that lines all blood vessels and is the sole constituent of capillary walls. It secretes tissue factor into extravascular tissues, and insulates those tissues from the hepatic enzymes, so that tissue disruption exposes tissue factor to the enzymatic interaction and activates tissue repair. The vascular endothelium also releases nitric oxide and von Willebrand Factor into blood in accord with autonomic balance to regulate the enzymatic interaction to govern tissue perfusion and organ function. Therefore, continuously fluctuating combinations of nervous stimuli that affect autonomic balance and forces that disrupt tissues determine SRM activity.

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“…The TF inhibitor (tissue factor pathway inhibitor, TFPI) is produced by EC (91) and it inhibits the complex FT/VIIa (91). The activity of TFPI has been associated with MS (92) and body mass index (BMI) (93).…”

Section: Alterations In Hemostasis and Fibrinolysismentioning

confidence: 99%

Hemostasis alterations in metabolic syndrome (Review)

Palomo¹,

Alarcón²,

Moore‐Carrasco³

et al. 2006

Int J Mol Med

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Abstract. Metabolic syndrome (MS) is characterized by the presence of at least three of the following alterations: enlargement of the waist diameter, higher levels of arterial pressure, low density lipoprotein cholesterol and glycemia, and reduction of high density lipoprotein cholesterol. The prevalence of MS reaches 23% in young adults, a percentage that increases with age. People with MS have a greater risk of suffering from cardiovascular disease (CVD). The physiopathologic alterations now found to exist in MS are diverse; among them is endothelial dysfunction, which triggers atherogenic lesions and hypercoagulability characterized by alterations of the coagulation factors and the regulatory proteins of fibrinolysis such as the plasminogen activator inhibitor (PAI-1). The increase in oxidative stress and/or the reactive oxygen species in patients with MS is partially related to the oxidation state of the lipoproteins, especially of the low density lipoproteins. This fact favors atherogenesis. Moreover, the oxidative stress produces alterations in the production of adipokines, cytokines secreted by the adipose tissues. The abnormality in the transport of lipoprotein diminishes the catabolism of the very low density lipoprotein (VLDL) and increases the catabolism of the high density lipoprotein (HDL), which creates insulin resistance. This process is associated with a lower concentration of adiponectin that in turn regulates the catabolism of VLDL and HDL; consequently increasing the flow of fatty acids from the adipose tissue to the liver and muscles. The proinflammatory cytokines, among them tumor necrosis factor · (TNF-·), are of great importance in MS regulating different processes and molecules such as PAI-1. PAI-1 is controlled by the group of transcription factors peroxisome proliferator-activated receptor (PPAR), especially by PPAR Á and · ligands. In summary, MS includes multiple alterations related to insulin resistance at several levels: hepatic, muscular, adipose and vascular tissue (endothelium). The exact mechanism that underlies the relationship between MS and CVD are not sufficiently known yet; pathogenic explanations are lacking for the mechanisms relating metabolic factors to insulin resistance and the association with the development of atherosclerosis and thrombosis. MS alterations and the main aspects related to homeostasis alterations are examined in this report.

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Tissue factor pathway inhibitors as a novel approach to antithrombotic therapy

Cited by 9 publications

References 0 publications

Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome

Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

Hemostasis alterations in metabolic syndrome (Review)

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