International Journal of Angiology最新文献

Venous thromboembolism (VTE) is a very frequent cardiovascular entity that encompasses deep vein thrombosis and pulmonary embolism (PE). This last entity represents a major cause of cardiovascular morbidity and mortality. The incidence of PE and the rate of PE-related morbidity significantly increase with age, race, and underlying medical conditions, such as malignancy. Given the recent advances in diagnostic strategies and algorithms, patients can be risk assessed and treated promptly to avoid disease progression. Anticoagulation is the mainstay of treatment for acute PE that is not hemodynamically unstable. Direct oral anticoagulants, such as apixaban, rivaroxaban, or edoxaban, are currently the preferred agents for the treatment of patients who present with acute PE or for long-term treatment. Treatment duration should be continued for at least 3 months, and all patients should be assessed for extended duration of therapy based on the precipitating factors that led to the development of the VTE. Novel anticoagulant agents targeting factor XI/XIa are currently being investigated in phases 2 and 3 clinical trials, representing an attractive option in anticoagulation therapies in patients with VTE. For hemodynamically unstable patients, systemic thrombolysis is the treatment of choice, and it may also be of benefit-in reduced dose-for patients with intermediate to high risk who are at risk of hemodynamic collapse.

Key to the diagnosis of pulmonary embolism (PE) is a careful bedside evaluation. After this, there are three further diagnostic steps. In all patients, estimation of the clinical probability of PE is performed. The other two steps are measurement of D-dimer when indicated and chest imaging when indicated. The clinical probability of PE is estimated at low, moderate, or high. The prevalence of PE is less than 15% among patients with low clinical probability, 15 to 40% with moderate clinical probability, and >40% in patients with high clinical probability. Clinical gestalt has been found to be very useful in estimating probability of PE. However, clinical prediction rules, such as Wells criteria, the modified Geneva score, and the PE rule out criteria have been advocated as adjuncts. In patients with high clinical probability, the high prevalence of PE can lower the D-dimer negative predictive value, which could increase the risk of diagnostic failure. Consequently, patients with high probability for PE need to proceed directly to chest imaging, without prior measurement of D-dimer level. Key studies in determining which low to moderate probability patients require chest imaging are the Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism (ADJUST-PE), the Simplified diagnostic management of suspected pulmonary embolism (YEARS), and the Pulmonary Embolism Graduated D-Dimer trials. In patients with low clinical probability, PE can be excluded without imaging studies if D-dimer is less than 1,000 ng/mL. In patients in whom there is not a low likelihood for PE, this can be excluded without imaging studies if the D-dimer is below the age-adjusted threshold.

Postoperative intimal hyperplasia is the major cause of the vein graft occlusion. It is very important to establish an animal model for the start of research. After my vascular surgery residency in Japan, I started my research work on postoperative intimal hyperplasia at the University of Wisconsin-Madison. My research showed that endothelial injury and monocyte infiltration is the key for postoperative intimal hyperplasia, which is very similar to Ross' pathogenesis of atherosclerosis as an inflammatory disease. Focusing on postoperative intimal hyperplasia as an inflammatory disease, especially on tumor necrosis factor-α, FR-167653 (tumor necrosis factor-α suppressive agent, inhibitor of p 38 mitogen-activated protein kinase; Fujisawa Pharmaceutical Co., Ltd., Japan) is found to suppress postoperative intimal hyperplasia in a rat model by reducing serum monocyte chemoattractant protein-1 levels. However, FR-167653 is not commercially available today. Because endothelial injury is the first step of postoperative intimal hyperplasia, I investigated whether the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Japan), which alleviates the endothelial injury in vitro , can also suppress postoperative intimal hyperplasia. Moreover, the free radical scavenger edaravone (Radicut®, Mitsubishi Tanabe Pharma Co.) is also found to suppress postoperative intimal hyperplasia, by alleviating endothelial injury. In clinical settings, it is very important to detect postoperative intimal hyperplasia before its establishment. Hepatocyte growth factor is not only a hepatic growth factor but also a vascular endothelial growth factor. Recently, serum hepatocyte growth factor level was found to be a candidate biomarker for postoperative intimal hyperplasia in our rat model.

Eukaryotic gene expression is linked to chromatin structure and nucleosome positioning by ATP-dependent chromatin remodelers that establish and maintain nucleosome-depleted regions (NDRs) near transcription start-sites. Conserved yeast RSC and ISW2 remodelers exert antagonistic effects on nucleosomes flanking NDRs, but the temporal dynamics of remodeler search, engagement and directional nucleosome mobilization for promoter accessibility are unknown. Using optical tweezers and 2-color single-particle imaging, we investigated the Brownian diffusion of RSC and ISW2 on free DNA and sparse nucleosome arrays. RSC and ISW2 rapidly scan DNA by one-dimensional hopping and sliding respectively, with dynamic collisions between remodelers followed by recoil or apparent co-diffusion. Static nucleosomes block remodeler diffusion resulting in remodeler recoil or sequestration. Remarkably, both RSC and ISW2 use ATP hydrolysis to translocate mono-nucleosomes processively at ~30 bp/sec on extended linear DNA under tension. Processivity and opposing push-pull directionalities of nucleosome translocation shown by RSC and ISW2 shape the distinctive landscape of promoter chromatin.