Background-Recently, thoracic aortic stent grafting has emerged as an alternative therapeutic modality for patients with thoracic aortic aneurysms and aortic dissections. However, its application has been limited to descending thoracic aortic aneurysms distal to the aortic arch. We report our initial clinical experience of endovascular branched stent graft repair for aortic arch aneurysms. Methods and Results-Endovascular grafting with Inoue branched stent grafts was attempted for 15 patients with thoracic aortic aneurysms and aortic dissections under local anesthesia (nϭ14) or general anesthesia (nϭ1). Single-branched stent grafts were used in 14 patients, and a triple-branched stent graft in one. The branched stent grafts were delivered through a 22F or a 24F sheath under fluoroscopic guidance and implanted across the aneurysmal aortic arch. In 2 patients, the single-branched stent graft did not pass through the 22F sheath used. Complete thrombosis of the aneurysm was ultimately achieved in 11 patients (73%). Of 4 persistent leaks, 1 minor leak spontaneously thrombosed and 1 major leak was successfully treated by additional straight stent graft placement. In 1 patient, the right external iliac artery ruptured during the withdrawal of the sheath and was successfully repaired by the implantation of a straight stent graft.One patient with severe stenosis of the aortic graft section was successfully managed by additional stent deployment. Peripheral microembolization to a toe occurred in 1 patient, and cerebral infarction occurred in 1 other patient. Two patients who had failed to receive endovascular stent grafts died during an average follow-up of 12.6 months, 1 of pneumonia and the other of rupture of a concomitant abdominal aortic aneurysm. Key Words: aneurysm Ⅲ vessels Ⅲ aorta Ⅲ stents Ⅲ grafting T he leading cause of death for patients with surgically untreated thoracic aortic aneurysms is ruptured aneurysm. [1][2][3] Currently, the standard treatment of thoracic aortic aneurysms is surgery with artificial graft replacement, for which perioperative mortality rates of 5% to 35% have been documented in multicenter reports. 4 -10 The surgical treatment has achieved remarkable advancement due to the introduction of deep hypothermic circulatory arrest and myocardial protection with cardioplegic solution. Despite recent progress of thoracic aortic surgery, complications are still prevalent in repair of aortic arch aneurysms, especially in patients with advanced age and coexisting morbid conditions. 4,11,12 Recently, catheter-based strategy for the treatment of coronary heart disease and valvular heart disease has progressed dramatically. 13 Therefore, the development of new, minimally invasive treatment for aortic aneurysms is desired. Conclusions-ThisTransluminal endovascular stent graft placement has recently been introduced as a promising alternative to surgical treatment of aortic aneurysms. For thoracic aortic aneurysms, Dake and colleagues first reported the clinical feasibility of endovascular repair with ...

Protein arginine methylation is a common posttranslational modification catalyzed by a family of the protein arginine methyltransferases (PRMTs). We have previously reported that PRMT1 methylates Forkhead box O transcription factors at two arginine residues within an Akt consensus phosphorylation motif (RxRxxS/T), and that this methylation blocks Akt-mediated phosphorylation of the transcription factors. These findings led us to hypothesize that the functional crosstalk between arginine methylation and phosphorylation could be extended to other Akt target proteins as well as Forkhead box O proteins. Here we identify BCL-2 antagonist of cell death (BAD) as an additional substrate for PRMT1 among several Akt target proteins. We show that PRMT1 specifically binds and methylates BAD at Arg-94 and Arg-96, both of which comprise the Akt consensus phosphorylation motif. Consistent with the hypothesis, PRMT1-mediated methylation of these two arginine residues inhibits Akt-mediated phosphorylation of BAD at Ser-99 in vitro and in vivo. We also demonstrate that the complex formation of BAD with 14-3-3 proteins, which occurs subsequent to Akt-mediated phosphorylation, is negatively regulated by PRMT1. Furthermore, PRMT1 knockdown prevents mitochondrial localization of BAD and its binding to the antiapoptotic BCL-X L protein. BAD overexpression causes an increase in apoptosis with concomitant activation of caspase-3, whereas PRMT1 knockdown significantly suppresses these apoptotic processes. Taken together, our results add a new dimension to the complexity of posttranslational BAD regulation and provide evidence that arginine methylation within an Akt consensus phosphorylation motif functions as an inhibitory modification against Akt-dependent survival signaling.

The results demonstrate the feasibility of the Inoue single-branched stent graft for thoracic aortic aneurysms or dissections involving the left subclavian artery.

Background-Although the MAZE procedure allows for the recovery of sinus rhythm and left atrial (LA) mechanical function in the great majority of patients with chronic atrial fibrillation (AF), the effects of MAZE on the precise LA geometry and wall motion remain to be elucidated. We hypothesized that LA size and mechanical function in patients with chronic AF and mitral valvular disease are well restored after MAZE. In the CABG group, LA maximal and minimal volumes and ejection fraction were 109Ϯ12 mL, 82Ϯ11 mL, and 26Ϯ10%, respectively. In the MAZE group, LA maximal volume was 139Ϯ17 mL (Pϭ0.187 versus CABG), and LA minimal volume was 121Ϯ16 mL (Pϭ0.082 versus CABG), with an ejection fraction of 15Ϯ7% (Pϭ0.004 versus CABG). In both groups, all parts of the LA wall contracted toward the geometric center of the LA. The extent of wall motion was significantly worse in the MAZE group compared with the CABG group. In both groups, LA booster function was inversely correlated with LA maximal volume. Conclusions-MAZE

Hepatic gluconeogenesis is important for the maintenance of blood glucose homeostasis under fasting condition. Hepatocyte nuclear factor 4α (HNF4α) and FOXO1 transcription factors have implicated in this process through transcriptional regulation of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), which are rate-limiting enzymes in gluconeogenesis. In this study, we demonstrate that glycogen synthase kinase 3β (GSK3β) regulates the expression of gluconeogenic genes through HNF4α and FOXO1. Silencing of GSK3β leads to reduction in the expression of gluconeogenic genes, including G6Pase, PEPCK, and peroxisome proliferator-activated receptor γ coactivator-1α. We show that GSK3β directly binds to both HNF4α and FOXO1. Inhibition of GSK3 by SB-216763 abolishes HNF4α-mediated activation of G6Pase promoter. We also found that overexpression of GSK3β potentiates G6Pase promoter activation by FOXO1 in a manner dependent on its kinase activity. Treatment of SB-216763 diminishes FOXO1-mediated activation of G6Pase promoter. Taken together, these results reveal a previously unrecognized mechanism for the regulation of gluconeogenic gene expression.