Inflammation and C-Reactive Protein in Atrial Fibrillation: Cause or Effect?

Atrial fibrillation is associated with substantial morbidity and mortality rates. The incompletely understood pathogenesis of this cardiac dysrhythmia makes it difficult to improve approaches to primary and secondary prevention. Evidence has accumulated in regard to a relationship between inflammation and atrial fibrillation. Investigators have correlated the dysrhythmia with myocarditis, pericardiotomy, and C-reactive protein levels, suggesting that inflammation causes atrial fibrillation or participates in its onset and continuation. Conversely, other investigators suggest that atrial fibrillation induces an inflammatory response. In this review, we summarize and critically discuss the nature and clinical role of inflammation and C-reactive protein in atrial fibrillation

Cirrhotic cardiomyopathy in the pre- and post-liver transplantation phase

Patients with advanced liver cirrhosis may develop a clinical syndrome characterized by a blunted contractile responsiveness to stress and/or altered diastolic relaxation, called "cirrhotic cardiomyopathy." This syndrome, which is initially asymptomatic, is often misdiagnosed due to the presence of symptoms that characterize other disorders present in patients with advanced liver cirrhosis, such as exercise intolerance, fatigue, and dyspnea. Stress and other conditions such as liver transplantation and transjugular intrahepatic portosystemic shunt (TIPS) may unmask this syndrome. Liver transplantation in this group of patients results in a clinical improvement and can be a cure for the cardiomyopathy. However, post-transplant prognosis depends on the identification of cirrhotics with cardiomyopathy in the pre-transplant phase; an early diagnosis of cirrhotic cardiomyopathy in the pre-transplant phase may avoid an acute onset or worsening of cardiac failure after liver transplantation. Since a preserved left ventricular ejection fraction may mask the presence of cirrhotic cardiomyopathy, the use of newer noninvasive diagnostic techniques (i.e. tissue Doppler, myocardial strain) is necessary to identify cirrhotics with this syndrome, in the pre-transplant phase. A pre-transplant treatment of heart failure in cirrhotics with cardiomyopathy improves the quality of life in this phase and reduces the complications during and immediately after liver transplantation. Since specific therapies for cirrhotic cardiomyopathy are lacking, due to the absence of a clear understanding of the pathophysiology of the cardiomyopathy, further research in this field is required

Targeting inflammation: Impact on atherothrombosis

Atherothrombosis is a worldwide epidemic accounting for an unacceptable toll of deaths and disabilities. Its pathophysiology is complex and hardly referable to a specific mechanism; however, in the last 20 years, a growing amount of evidence has demonstrated that inflammatory processes play a major role from the very beginning to the ultimate complication of atherothrombosis. These evidences are addressing a growing interest toward anti-inflammatory agents as preventive or curative treatments of atherothrombosis. At present, accumulated data are not conclusive, but strong evidence exists in favor of an anti-inflammatory positive effect for several drugs as statins or renin-angiotensin inhibitors. More conclusive data are expected from ongoing trials directly exploring the role of specific cytokines antagonists. © 2013 Springer Science+Business Media New York

Analysis of detergent-resistant membranes associated with apical and basolateral GPI-anchored proteins in polarized epithelial cells.

Detergent-resistant membranes (DRMs) represent specialized membrane domains resistant to detergent extraction, which may serve to segregate proteins in a specific environment in order to improve their function. Segregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs) in DRMs has been shown to be involved in their sorting to the apical membrane in polarized epithelial cells. Nonetheless, we have shown that both apical and basolateral GPI-APs associate with DRMs. In this report we investigated the lipid composition of DRMs associated with an apical and a basolateral GPI-AP. We found that apical and basolateral DRMs contain the same lipid species although in different ratios. This specific lipid ratio is maintained after mixing the cells before lysis indicating that DRMs maintain their identity after Triton extraction

Inflammatory markers in STelevation acute myocardial infarction

After acute myocardial infarction, ventricular remodeling is characterized by changes at the molecular, structural, geometrical and functional level that determine progression to heart failure. Inflammation plays a key role in wound healing and scar formation, affecting ventricular remodeling. Several, rather different, components of the inflammatory response were studied as biomarkers in ST-elevation acute myocardial infarction. Widely available and inexpensive tests, such as leukocyte count at admission, as well as more sophisticated immunoassays provide powerful predictors of adverse outcome in patients with ST-elevation acute myocardial infarction. We review the value of inflammatory markers in ST-elevation acute myocardial infarction and their association with ventricular remodeling, heart failure and sudden death. In conclusion, the use of these biomarkers may identify subjects at greater risk of adverse events and perhaps provide an insight into the mechanisms of disease progression

Sphingosine Kinase Mediates Resistance to the Synthetic Retinoid N-(4-Hydroxyphenyl)retinamide in Human Ovarian Cancer Cells*

A2780 human ovarian carcinoma cells respond to treatment with the synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) with the production of dihydroceramide and with a concomitant reduction of cell proliferation and induction of apoptosis. The derived HPR-resistant clonal cell line, A2780/HPR, is less responsive to HPR in terms of dihydroceramide generation. In this report, we show that the production of sphingosine 1-phosphate (S1P) is significantly higher in A2780/HPR versus A2780 cells due to an increased sphingosine kinase (SK) activity and SK-1 mRNA and protein levels. Treatment of A2780 and A2780/HPR cells with a potent and highly selective pharmacological SK inhibitor effectively reduced S1P production and resulted in a marked reduction of cell proliferation. Moreover, A2780/HPR cells treated with a SK inhibitor were sensitized to the cytotoxic effect of HPR, due to an increased dihydroceramide production. On the other hand, the ectopic expression of SK-1 in A2780 cells was sufficient to induce HPR resistance in these cells. Challenge of A2780 and A2780/HPR cells with agonists and antagonists of S1P receptors had no effects on their sensitivity to the drug, suggesting that the role of SK in HPR resistance in these cells is not mediated by the S1P receptors