Chronic Diseases

The thromboxane A2 pathway through its end product thromboxane A2 is implicated in the development and progression of many chronic diseases. There is clear clinical and/or experimental evidence platelet thromboxane A2 release is greatly enhanced in a number of chronic diseases. Frequently in these diseases, the balance between thromboxane A2 and prostacyclin is significantly altered, resulting in excessive vasoconstriction and disorders of hemostasis. Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway resulting in thromboxane A2 generation.

Relationship of PCSK9 and urinary Thromboxane Excretion to Cardiovascular Events in Patients with Atrial Fibrillation

"Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available. This study investigated the association between PCSK9 and CVEs in AF; as well as, the relationship between PCSK9 and urinary 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation. Plasma PCSK9 levels are associated with an increased risk of CVEs in patients with AF. The direct correlation between PCSK9 and 11-dh-TxB2 suggests PCSK9 as a mechanism potentially implicated in platelet activation."

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Inhibiting breast cancer by targeting the thromboxane A2 pathway

“Cyclooxygenases have been implicated in mammary tumorigenesis. We sought to identify the key prostaglandin responsible for the pro-neoplastic effect of cyclooxygenases and develop prostaglandin-targeted strategies for breast cancer chemoprevention or therapy."

“Clinically, the thromboxane A2 pathway might be associated with HER2- positive and axillary lymph node metastasis in human breast cancer. We found that the thromboxane A2 pathway was required for breast cancer cell growth, anchorage-independent growth and invasion capabilities."

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Urinary 11-dehydro-thromboxane B2 and mortality in patients with stable coronary artery disease

"Urinary concentration of 11DHTXB2 was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures."

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Urinary 11-dehydro-thromboxane B2 as a predictor of acute myocardial infarction outcomes: results of leukotriene and thromboxane in myocardial infarction (LTMI) study

"Urinary 11-dehydro-thromboxane (TX)B2 has been described as a potential predictive biomarker of major adverse cardiovascular events (MACEs) in high cardiac risk patients.”

“11-Dehydro-TXB2 predicts 1-year cumulative MACEs in AMI patients and provides prognostic information on the left ventricular performance."

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Urinary 11-Dehydro-Thromboxane B2: A Novel Thrombosis Risk Marker in LVAD Recipients

"Urinary 11-dehydrothromboxane B2 (UTBx) was associated with an increased risk of thrombotic events in two major clinical trials of cardiovascular disease. The utility of UTBx as a thrombotic risk marker in patients treated with a left ventricular assist device (LVAD) is unknown. In this first report the serial assessment of UTBx and measurement of UTBx at the time of adverse event occurrence in LVAD recipients, UTBx was associated with aspirin dose, bleeding and thrombotic events."

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Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus

"Resistin is an adipokine that promotes inflammation and insulin resistance by targeting several cells including platelets. We hypothesised that in type 2 diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane-dependent platelet activation and platelet-derived inflammatory proteins release, key determinants of atherothrombosis. Age and gender adjusted serum resistin levels were significantly higher in patients than in controls. HOMA and 11-dehydro-TXB2 independently predicted resistin levels."

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Impact of commonly prescribed exercise interventions on platelet activation in physically inactive and overweight men

"The exercise paradox infers that, despite the well-established cardioprotective effects of repeated episodic exercise (training), the risk of acute atherothrombotic events may  be transiently increased during and soon after an exercise bout.  However, the acute impact of different exercise modalities on platelet function has not previously been addressed.  We hypothesized that distinct modalities of exercise would have differing effects on in vivo platelet activation and reactivity to agonists which induce monocyte-platelet aggregate (MPA) formation."

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Statin therapy and inflammation in patients with diabetes treated with high dose aspirin

"Statin and aspirin form the therapeutic cornerstone in patients with coronary artery disease and diabetes.  Little is known about relationship of statins with blood thrombogenicity and inflammation in these patients."

"Statins along with aspirin, confers additional anti-inflammatory and antithrombotic effect in diabetics with CAD. Urinary 11-DHTXB2 may be a useful biomarker for personalizing statin therapy."

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Aspirin use and reduced risk of pancreatic cancer

"Few options besides the avoidance of smoking and obesity are available to prevent pancreatic cancer.  The association between aspirin use and risk of pancreatic cancer has been inconsistent across studies.  

"Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half."

"People who take aspirin for prevention of other diseases likely also reduce their risk of pancreatic cancer.  Aside from benefits for both cardiovascular disease and certain cancers, long term aspirin use entails some risks of bleeding complications, which necessitates risk-benefit analysis for individual decisions about use."

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Curcumin anticancer studies in pancreatic cancer

"Pancreatic cancer is one of the deadliest cancers woldwide.  Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis"

"We also demonstrated that curcumin inhibited the proliferation and enhanced the apoptosis of MIA PaCA-2 cells, through the suppression of NF-kB-activation."

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