endothelin-1 and Blood-Coagulation-Disorders

Vascular endothelial dysfunction refers to a loss of normal homeostatic functions in the blood vessels. It is characterized by reduced vasodilation and enhanced vasoconstriction functions and chronic prothrombotic and inflammatory activity. There is convincing evidence for endothelial dysfunction in obstructive sleep apnea (OSA): OSA is associated with alterations in vascular structures and their elastic properties, increased circulating cell-derived microparticles, reduced endothelial repair capacity, and vascular reactivity. These alterations may be related to the reduced availability of nitric oxide, which has major vasoprotective effects including vasodilation, inhibition of platelet adhesion and aggregation, inhibition of leukocyte-endothelial adhesion and inhibition of smooth muscle cell proliferation. It is unknown whether endothelial dysfunction in OSA is due to alterations in vasoconstriction mechanisms related to angiotensin II or endothelin 1. In OSA, endothelial dysfunction may be related to chronic intermittent hypoxia and to sleep loss and fragmentation. These conditions may increase the levels of various markers of inflammation and oxidative stress, as well as those of increased procoagulant and thrombotic activity. In addition, they may produce an imbalance of vasomotor function. Endothelial dysfunction contributes to the development of atherosclerosis and cardiovascular disorders associated with OSA. However, other diseases that are also associated with endothelial dysfunction are OSA comorbidities, e.g. obesity, insulin resistance, smoking habits and cardiovascular diseases such as hypertension and coronary artery disease. This makes it difficult to demonstrate a causal link between OSA and endothelial dysfunction; nevertheless, evidence for such a link has been produced by therapeutic studies. The administration of continuous positive airway pressure may reverse changes associated with endothelial dysfunction and, therefore, may decrease the risk of cardiovascular disease in OSA patients.

Topics: Adult; Angiotensin II; Apoptosis; Biomarkers; Blood Coagulation Disorders; Cardiovascular Diseases; Continuous Positive Airway Pressure; Endothelin-1; Endothelium, Vascular; Humans; Nitric Oxide; Oxidative Stress; Risk Factors; Sleep Apnea, Obstructive

The aim of the present paper is to analyze recent literature concerning the incidence of cardiovascular complications in women suffering from polycystic ovary syndrome (PCOS). The study takes into consideration all the studies that have been published to date in the international literature in order to clarify whether or not PCOS is able to determine an early onset or whether it is responsible for a higher global incidence of cardiovascular complications in adult age. The main difficulty lies in the absence of prospective studies owing to the long period of time existing between the diagnosis of PCOS and cardiovascular disease which notoriously has a long latency period. Much attention has been paid in the literature, on the other hand, to the analysis of the incidence of cardiovascular risk factors in women suffering from PCOS. Although epidemiological studies have not evidenced an increased incidence of death from cardiovascular events in women suffering from PCOS, the above conclusions might well be invalidated by a patient selection bias, by obsolete diagnostic criteria or by medical or surgical therapies that could influence the outcome of the disease and which are not considered as a confusion factor. Undoubtedly, all the data available up to the present suggest that PCOS possesses the intrinsic conditions that lead to an increased incidence of factors predisposing to cardiovascular diseases. Future longitudinal studies of a prospective nature might be useful for understanding whether the higher incidence of predisposing factors might also lead to greater expectation of cardiovascular events or whether medical therapies or other factors (improvement in endocrine symptomatology with the menopause?) may prevent the increase in the expected incidence of these events.

Topics: Biomarkers; Blood Coagulation Disorders; Cardiovascular Diseases; Carotid Stenosis; Endothelin-1; Endothelium, Vascular; Female; Humans; Hyperlipidemias; Hypertension; Incidence; Menstrual Cycle; Myocardial Ischemia; Polycystic Ovary Syndrome; Risk Factors

Recent investigations have associated airborne particulate matter (PM) with increased coagulation and thrombosis, but underlying biological mechanisms are still incompletely characterised. DNA methylation is an environmentally sensitive mechanism of gene regulation that could potentially contribute to PM-induced hypercoagulability. We aimed to test whether altered methylation mediates environmental effects on coagulation.. We investigated 63 steel workers exposed to a wide range of PM levels, as a work-related condition with well-characterised prothrombotic exposure. We measured personal PM10 (PM≤10 µm in aerodynamic diameter), PM1 (≤1 µm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitric-oxide-synthase-3) and EDN1 (endothelin-1) through bisulfite-pyrosequencing and we measured ETP as a global coagulation-activation test after standardised triggers.. ETP increased in association with PM10 (β=20.0, 95% CI 3.0 to 37.0), PM1 (β=80.8 95% CI 14.9 to 146.7) and zinc (β=51.3, 95% CI 0.01 to 111.1) exposures. NOS3 methylation was negatively associated with PM10 (β=-0.2, 95% CI -0.4 to -0.03), PM1 (β=-0.8, 95% CI -1.4 to -0.1), zinc (β=-0.9, 95% CI -1.4 to -0.3) and iron (β=-0.7, 95% CI -1.4 to -0.01) exposures. Zinc exposure was negatively associated with EDN1 (β=-0.3, 95% CI -0.8 to -0.1) methylation. Lower NOS3 (β=-42.3; p<0.001) and EDN1 (β=-14.5; p=0.05) were associated with higher ETP. Statistical mediation analysis formally confirmed NOS3 and EDN1 hypomethylation as intermediate mechanisms for PM-related coagulation effects.. Our study showed for the first time, that gene hypomethylation contributes to environmentally induced hypercoagulability.

Topics: Adult; Air Pollutants; Blood Coagulation; Blood Coagulation Disorders; Confidence Intervals; DNA Methylation; Endothelin-1; Gene Expression Regulation; Humans; Industry; Inflammation; Inhalation Exposure; Leukocytes; Male; Middle Aged; Nitric Oxide Synthase Type III; Occupational Diseases; Occupational Exposure; Particulate Matter; Thrombosis; Zinc

In this article, the authors discuss three pathophysiologic mechanisms that influence the coagulation system in patients who have liver disease. First, bacterial infections may play an important role in the cause of variceal bleeding in patients who have liver cirrhosis, affecting coagulation through multiple pathways. One of the pathways through which this occurs is dependent on endogenous heparinoids, on which the authors focus in this article. Secondly, the authors discuss renal failure, a condition that is frequently encountered in patients who have liver cirrhosis. Finally, they review dysfunction of the endothelial system. The role of markers of endothelial function in cirrhotic patients, such as von Willebrand factor and endothelin-1, is discussed.

Topics: Bacterial Infections; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Endothelin-1; Endothelium, Vascular; Heparinoids; Humans; Liver Cirrhosis; Renal Insufficiency; Varicose Veins; von Willebrand Factor