Category Archives: Thrombin

Thrombin, Inflammation, and Cardiovascular Disease: Conclusions

Thrombin, Inflammation, and Cardiovascular Disease: ConclusionsThis statistical association may be mediated by the key proinflammatory cytokine (also an adipokine) TNF-a, which is a so-called first-wave cytokine influencing IL-6 production, as well as many other cellular functions. TNF-a receptor (TNFR) I signals programmed cell death, while TNFR II may signal survival or proliferation through cytoplasmic TNFR-associated proteins, which can both negatively regulate apoptosis and positively promote survival. Although the role (if any) of circulating TNF-a in humans remains uncertain, TNF-a induces insulin resistance in tissue culture and in animal models.’ Plasma levels are also elevated in the metabolic syndrome, and are associated with insulin resistance in humans. fully

Thrombin, Inflammation, and Cardiovascular Disease: Inflammatory cytokines

The exact mechanism for the association of CRP with coagulation status is not clear; however the work of Ritchie and colleagues suggests a possible pathway. Monocytes appear capable of binding FDPs and subsequently producing IL-6, which goes to the liver and affects the wide range of proteins known to be in the acute-phase response. This has been proposed to be the mechanism by which fibrinogen consumption is replaced, and may be an important mechanism connecting coagulation and inflammation. This theory may have far-reaching implications both in the general biology we have been discussing and in such areas as drug development, where the coagulation-inflammation connection in sepsis, as described by Esmon et al, has been recently exploited. Reading here

Thrombin, Inflammation, and Cardiovascular Disease: Metabolic Syndrome

Thrombin, Inflammation, and Cardiovascular Disease: Metabolic SyndromeIn some cases, there are significant differences in the strengths of association. Also, each marker may participate in the CVD process in a different way. In a side-by-side comparison, CRP had the strongest risk prediction, but a meta-analysis observed no real difference between CRP and fibrinogen in risk prediction.
Inflammation and the Metabolic Syndrome: an Important Relationship
It has been observed that markers of inflammation are associated with the components of the metabolic syn-drome; this finding is in addition to the known association of inflammation markers, as well as markers of coagulant activity, with diabetes status. there

Thrombin, Inflammation, and Cardiovascular Disease: Risk prediction to CRP

However, a wide variety of activities, such as innate immunity, coagulation, and others, fall under the term inflammation. Each of these activities plays an important role in our response to trauma and/or environmental challenge: coagulation and fibrinolysis in restricting blood loss and in wound repair; complement activation and T-cell differentiation as part of innate and adaptive immunity; endothelial cell, neutrophil, and monocyte activation in immunity and wound repair; antioxidation in response to oxidative challenge; and others. In addition, variances in the genes responsible for the overall regulation of this system may play important roles in disease susceptibility; eg, IL-6 and tumor necrosis factor (TNF)-a genes.

Thrombin, Inflammation, and Cardiovascular Disease: CRP or fibrinogen

Thrombin, Inflammation, and Cardiovascular Disease: CRP or fibrinogenWe should note that “inflammation” as the term is used here does not mean the full form of the condition (warmth, redness, swelling, and pain), but rather implies a “micro-inflammation.” A person with this condition is characterized by being in the upper part of the “normal” distribution for inflammation status, without the signs and symptoms of overt, clinical inflammation. Molecular epidemiology has played a key role in identifying the role of inflammation in CVD, and recently it has become clear that inflammation is connected to the metabolic syndrome in a complex and important manner. Link

Thrombin, Inflammation, and Cardiovascular Disease: Inflammation Markers and CVD Risk

PAI-1 levels are associated with insulin, suggesting that the role of PAI-1 may be particularly important in people with the metabolic syndrome or type 2 diabetes. The regulation of PAI-1 levels—at least in blood—is in part mediated by regulators of glycemic control and inflammation: insulin and proinsulin can stimulate endothelial cells and hepatocytes to produce PAI-1,’ and PAI-1 is believed to be a weak acute-phase reactant. In addition, adipocytes can directly synthesize and secrete PAI-1, helping to explain the known association of PAI-1 levels with body mass index. this

Thrombin, Inflammation, and Cardiovascular Disease: Atherothrombosis

Thrombin, Inflammation, and Cardiovascular Disease: AtherothrombosisWhile it remains unproven whether any of these mechanisms are actually at play in situ, given all the available data it seems likely that higher fibrinogen may well not only reflect the low-grade inflammation caused by the atherothrombosis, but also participate in that process, allowing it to proceed at a faster rate. This “positive feedback” is illustrated in Figure 1.

Thrombin, Inflammation, and Cardiovascular Disease: CVD risk

To support this position, studies of the plasma levels of prothrombin (a key procoagulant protein, but not an inflammation-sensitive protein) and/or the prothrombin G20210A genotype associated with plasma levels, generally have been null for CVD risk in most cases while consistently positive for venous thrombosis. Also, several studies have examined the anticoagulant proteins and their relationship to CVD. As an ancillary study to the Thrombolysis in Myocardial Infarction Phase II trial of thrombolytic therapy, we demonstrated that in those entering the health system with MIs, anticoagulant proteins, such as protein C and antithrombin, were elevated, not decreased. We have also demonstrated that in otherwise healthy adults tissue factor pathway inhibitor levels were higher, not lower, in those with increased measures of subclinical disease based on ankle-brachial BP index and carotid ultrasonography.

Thrombin, Inflammation, and Cardiovascular Disease: Atherosclerosis, Thrombosis, and Inflammation

Thrombin, Inflammation, and Cardiovascular Disease: Atherosclerosis, Thrombosis, and InflammationThere Is a Complex Interplay Among Atherosclerosis, Thrombosis, and Inflammation
Atherosclerotic coronary heart disease commonly manifests itself clinically via a thrombotic event: so-called “atherothrombosis,” especially in younger men. As mentioned above, this has been clearly understood only since the early 1970s. As an overview, the process of blood clotting is comprised of coagulation, limited and controlled by anticoagulation; and the counterbalancing process of fibrinolysis, limited and controlled by antifibrinolysis. more

Thrombin, Inflammation, and Cardiovascular Disease: Thrombotic disease

Overall, a meta-analysis demonstrated moderate risk prediction for d-dimer. The most likely interpretation of these data are that the degree of atherosclerosis and vascular damage causes changes in coagulation status, not vice versa; ie, it does not appear that a preexisting hypercoag-ulable state is in the causal pathway of atherosclerotic disease and CVD events. This position is supported by the findings such as those of Lowe et al, in which future ischemic events were predicted by d-dimer levels but not by other markers of procoagulant activity, such as prothrombin fragment F1 + 2 and thrombin-antithrombin complex (measures of thrombin generation), or by factor VII coagulant activity (factor VIIc, which at least partly reflects factor VII activation). Link

Pages: 1 2 Next