Uric acid plasma levels are associated with C-reactive protein concentrations and the extent of coronary artery lesions in patients with acute coronary syndromes.

Many studies have pointed out that inflammation plays a pivotal role in pathophysiology of acute coronary syndromes (ACS) because several inflammatory molecules impair the endothelial functions in the coronary circulation and promote atherothrombotic events. Recently, many clinical/experimental evidences indicate that elevated plasma levels of uric acid (UA) might be considered a risk factor for developing ACS. It has been reported that elevated UA doses impair physiologic functions of endothelial cells, shifting them toward a pro atherothrombotic phenotype. In the present manuscript, we investigated the relationship between UA plasma levels, inflammatory burden, and extension of coronary atherosclerotic disease in patients with ACS. Patients with a clinical presentation of ACS (ST-elevated and non-ST-elevated myocardial infarction) admitted to the Vanvitelli Catheterization Laboratory at Monaldi Hospital in 2019, before the COVID-19 pandemia, were retrospectively analyzed. Biochemical profile, type of ACS presentation, as well as extension of coronary atherosclerosis were assessed. A total of 132 ACS patients were included in the analysis, and grouped into 3 tertiles according to the UA values (UA < 4.72 mg/dl, UA between 4.72 and 6.15 mg/dl, and UA > 6.15 mg/dl). Patients with UA plasma levels ≥ 6.15 mg/dL showed higher levels of C-reactive protein (mean of 5.1 mg/dL) as compared to patients with lower UA plasma levels. Moreover, the former group of patients showed higher levels of cardiac troponin and CPK, and presented more often with multivessel disease and complex coronary stenosis (type C of Ellis classification). Even though monocentric and with limited sample size, the present study shows that plasma levels of UA and hs-CRP are elevated in ACS patients and are associated with a more severe coronary disease, suggesting a potential role of UA in the pathophysiology of acute coronary events.

Uric Acid Induces a Proatherothrombotic Phenotype in Human Endothelial Cells by Imbalancing the Tissue Factor/Tissue Factor Pathway Inhibitor Pathway.

BACKGROUND: Several evidence show that elevated plasma levels of uric acid (UA) are associated with the increased risk of developing atherothrombotic cardiovascular events. Hyperuricemia is a risk factor for endothelial dysfunction (ED). ED is involved in the pathophysiology of atherothrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the tissue factor (TF)/TF pathway inhibitor (TFPI) balance by finally changing the antithrombotic characteristics of endothelial cells. METHODS: Human umbilical vein endothelial cells were incubated with increasing doses of UA (up to 9 mg/dL). TF gene and protein expressions were evaluated by real-time polymerase chain reaction (PCR) and Western blot. Surface expression and procoagulant activity were assessed by FACS (fluorescence activated cell sorting) analysis and coagulation assay. The mRNA and protein levels of TFPI were measured by real-time PCR and Western blot. The roles of inflammasome and nuclear factor-κB (NF-κB) as possible mechanism(s) of action of the UA on TF/TFPI balance were also investigated. RESULTS: UA significantly increased TF gene and protein levels, surface expression, and procoagulant activity. In parallel, TFPI levels were significantly reduced. The NF-κB pathways appeared to be involved in modulating these phenomena. Additionally, inflammasome might also play a role. CONCLUSION: The present in vitro study shows that one of the mechanisms by which high levels of UA contribute to ED might be the imbalance between TF/TFPI levels in endothelial cells, shifting them to a nonphysiological, prothrombotic phenotype. These UA effects might hypothetically explain, at least in part, the relationship observed between elevated plasma levels of UA and cardiovascular events.

Effects of colchicine on tissue factor in oxLDL-activated T-lymphocytes.

Several studies have shown that T-cells might be involved in pathophysiology of acute coronary syndromes (ACS). Tissue factor (TF) plays a key role in ACS. Many evidences have indicated that some statins reduce TF expression in several cell types. However, literature about rosuvastatin and TF and about statins effects on T-cells is still scanty. Colchicine is an anti-inflammatory drug recently proven to have beneficial effects in ACS via unknown mechanisms. This study investigates the effects of colchicine and rosuvastatin on TF expression in oxLDL-activated T-cells. T-cells, isolated from buffy coats of healthy volunteers, were stimulated with oxLDL (50 µg/dL). T-cells were pre-incubated with colchicine (10 µM) or rosuvastatin (5 µM) for 1 h and then stimulated with oxLDL (50 µg/mL). TF gene (RT-PCR), protein (western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. NF-κB/IκB axis was examined by western blot analysis and translocation assay. Colchicine and rosuvastatin significantly reduced TF gene, and protein expression and procoagulant activity in oxLDL stimulated T-cells. This effect was associated with a significant reduction in TF surface expression as well as its procoagulant activity. These phenomena appear modulated by drug effects on the transcription factor NF-kB. Rosuvastatin and colchicine prevent TF expression in oxLDL-stimulated T-cells by modulating the NF-κB/IκB axis. Thus, we speculate that this might be another mechanism by which these drugs exert benefic cardiovascular effects.

A rare case of deep vein and right atrial thrombosis in a patient with chronic heart failure and pulmonary embolism.

Deep vein thrombosis (DVT) is frequently observed in patients with chronic heart failure (CHF), increasing the risk of pulmonary embolism (PE). Clinical evaluation of CHF patients with suspected acute PE is challenging since these diseases share several symptoms and signs such as dyspnea. Thus, it is intuitive that correct and fast diagnosis of PE in these patients might be able to significantly change their clinical outcome. In the present report, we describe a rare case of a patient with CHF and PE due to a huge thrombosis of deep veins and of right atrium in whom echo evaluation permitted the correct diagnosis and therapy.