Kentaro Takaji

Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis

Background— Transplantation of endothelial progenitor cells has been proposed as a potential strategy for therapeutic revascularization. However, the limited endogenous cell pool and the related technical difficulties constitute clinically important disadvantages to autologous transplantation. In this study we investigated whether fully differentiated endothelial cells (ECs) modified with gene transfer of Id1, a helix-loop-helix transcription factor involved in angiogenesis, have the potential to contribute to therapeutic angiogenesis. Methods and Results— The Id1 gene was transferred into human umbilical vein ECs (HUVECs) via a Sendai virus vector. Id1 stimulated migration, proliferation, and capillary-like tube/cord formation of HUVECs. In addition, Id1 reduced serum deprivation–induced HUVEC apoptosis, as shown by FACS analysis with annexin V and TUNEL staining. Transplantation of Id1-overexpressing HUVECs accelerated recovery of blood flow as evaluated by laser-Doppler perfusion imaging, increased capillary density, and improved the rate of limb salvage compared with the transplantation of control HUVECs. Histochemical analysis revealed that the regenerated vascular networks of limbs transplanted with Id1-overexpressing HUVECs contained numerous HUVECs, some of which were in a proliferative state. Untransfected HUVECs were also incorporated with Id1-transfected HUVECs, suggesting the noncell autonomous effect of Id1. Finally, angiopoietin-1 was upregulated in Id1-overexpressing HUVECs and functionally contributed to the in vitro angiogenic effect of Id1. Conclusions— Id1 gene transfer conferred HUVECs with an angiogenic property, contributing to neovascularization after transplantation into ischemic lesions. Transplantation of Id1-overexpressing mature ECs may serve as a novel and useful strategy for therapeutic angiogenesis.

Protein kinase A-regulated nucleocytoplasmic shuttling of Id1 during angiogenesis.

Id1, an inhibitory partner of basic-helix-loop-helix transcriptional factors, has recently been recognized as a potent contributor to angiogenesis. However, the molecular mechanism underlying its role in angiogenesis remains essentially unknown. Herein we demonstrate the subcellular localization of Id1 to be altered depending on the cellular context of vascular endothelial cells. Id1 was localized in the nuclei of human umbilical vein endothelial cells (HUVECs) cultured on uncoated plates, whereas it was translocated to the cytoplasm in HUVECs on Matrigel along with the formation of capillary-like structures. Treatment with the nuclear export inhibitor leptomycin B and mutagenesis analysis using green fluorescent protein-fused Id1 revealed CRM1/exportin-dependent nuclear export of Id1 in HUVECs on Matrigel. This nuclear export of Id1 was inhibited by protein kinase A (PKA) activation by dibutyryl cyclic AMP and forskolin but was promoted by PKA inactivation by H-89 and MDL-12,330A. Mutagenesis analysis of Id1 showed the phosphorylation of Ser-5 to possibly mediate the effect of PKA. These results suggest the function of Id1 as a transcriptional factor to be controlled by nucleocytoplasmic shuttling during angiogenesis and that PKA might be involved in this process. This may serve as a novel mechanism regulating angiogenesis and as a possible target for therapeutic vascular regeneration.

Predictive factors for platelet number after cardiopulmonary bypass and postoperative blood loss

We retrospectively searched for factors that can predict the circulating platelet count after cardiopulmonary bypass (CPB) and postoperative blood loss. Correlations between the circulating platelet count after CPB and several other perioperative variables were investigated in 42 patients who underwent cardiac surgery using the same type of oxygenator. Correlations between perioperative variables and 24 hour postoperative blood loss were also investigated. A multiple stepwise regression analysis showed that the preoperative platelet count, age, and intraoperative blood transfusion values were independent predictors of the circulating platelet count after CPB (R2 = 0.661, p < 0.0001). Gender, operation type, and priority (elective or urgent) were not associated with the platelet count after CPB or postoperative blood loss. Independent predictive factors for postoperative blood loss consisted of age and intraoperative blood loss (R2 = 0.231, p = 0.006). In addition to preoperative platelet count, age and amount of intraoperative blood transfusion are predictive factors for circulating platelet count after CPB. The association of postoperative blood loss with age and intraoperative blood loss may suggest friability of the tissues, including blood vessels, in elderly patients.

A simple method of intraoperative preparation of a stent graft for distal aortic arch aneurysm

J Thorac Cardiovasc Surg Takaji, Yukihiro Katayama and Michio Kawasuji Ryuji Kunitomo, Shigeyuki Tsurusaki, Hisashi Sakaguchi, Ichiro Ideta, Kentaro arch aneurysm A simple method of intraoperative preparation of a stent graft for distal aortic http://jtcs.ctsnetjournals.org/cgi/content/full/125/6/1535 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Use of the Konno Procedure in an 80-year-old Woman with Aortic Stenosis, a Narrow Left Ventricular Outflow Tract, and a Small Aortic Annulus

This report describes a technique for repairing an aortic stenosis in an elderly patient with a small aortic annulus and a narrow left ventricular outflow tract. Preoperative echocardiography in an 80-year-old woman showed severe aortic stenosis with a narrow outflow tract: the aortic valve area was 0.48 cm(2), the aortic annular diameter was 14 mm, and the left ventricular outflow tract diameter was 14 mm. The Konno procedure was used to enlarge both the small aortic annulus and the left ventricular outflow tract, and a 19-mm Carpentier-Edwards bioprosthetic valve was implanted. The patients postoperative course was uneventful. The left ventricular mass decreased from a preoperative value of 236 g to 96 g, 3 years after surgery. Only a few reports have described the use of the Konno operation in adult patients. In the present case, the Konno operation was demonstrated to be a good option for aortic stenosis accompanied by a small aortic annulus and a narrow left ventricular outflow tract, even in an elderly patient.

A Case Report of Double Valve Replacement for Mucopolysaccharosis with Chest Pain Attack and Severe Heart Failure

今回われわれはムコ多糖症に対する2弁置換術の1例を経験したので報告する.症例は27歳女性,11歳時よりムコ多糖症を疑われていたが,平成13年9月ころより連合弁膜症による心不全症状と胸痛発作が出現し,手術目的で当科に紹介された.心エコーおよび心臓カテーテル検査上,IV度の大動脈弁閉鎖不全症とIII度の僧帽弁閉鎖不全症が認められた.手術は2弁置換術を施行し,術後経過順調で術後38日目に退院となった.術前の尿検査でヘパラン硫酸陽性を示したが,リンパ球酵素活性は正常でムコ多糖症の確定診断にはいたらなかった.しかし,摘出した大動脈弁弁尖と僧帽弁弁尖の組織所見上はムコ多糖の高度沈着を認め,臨床所見も含めるとムコ多糖症による心臓連合弁膜症と考えられた.