Background-Pulmonary hypertension (PH) is a life-threatening disease. Bone marrow cell transplantation is reported to reduce the development of PH by increasing vascular beds in pulmonary circulation. However, adenoviral overexpression of endothelial nitric oxide synthase (eNOS) in the lung is also known to reduce PH. Because mesenchymal stem cells (MSCs) are potential cell sources for neovascularization, the implantation of MSCs overexpressing eNOS (MSCs/eNOS) may further improve the surgical results. We evaluated the efficacy of MSCs/eNOS implantation in monocrotaline (MCT)-induced PH rats. Methods and Results-MSCs were isolated from rat bone marrow. PH was induced in rats by subcutaneous injection of MCT. One week after MCT administration, the rats received 3 different treatments: MSCs (MSC group), MSCs/eNOS (MSC/eNOS group), or nontreatment (PH group). As the negative control, rats received saline instead of MCT (control group). Right ventricular (RV) hypertrophy and the elevation of RV systolic pressure (RVSP) were evaluated 3 weeks after MCT administration. Moreover, the effects of MSCs/eNOS on survival were investigated in PH induced by MCT 3 weeks earlier. RVSP in both the MSC and MSC/eNOS groups was significantly lower than the PH group. RVSP in the MSC/eNOS group was significantly lower than the MSC group. The RV weight to body weight ratio was significantly lower in the MSC and MSC/eNOS groups than the PH group. The survival time of rats receiving MSCs/eNOS was significantly longer than the nontreatment rats. Conclusion-Intravenous

Cardiac blood cysts are rarely seen in adult patients and in the right atrium. The origin of cardiac blood cysts is not understood, and several hypotheses have been proposed. We present a rare case of right atrial blood cyst with total occlusion of the right coronary artery (RCA). Inflammatory processes may have played an important role in the development of the cyst, because infiltration of inflammatory cells was observed in the cystic wall. Additionally, total obstruction of the proximal RCA indicated that ischemia and/or infarction in the right atrium might be related to formation of the cyst.

Background-Endothelial dysfunction is known to exaggerate coronary artery disease, sometimes leading to irreversible myocardial damage. In such cases, repetitive coronary revascularization including coronary artery bypass grafting is needed, which may cause a shortage of graft conduits. On the other hand, endothelial nitric oxide synthase (eNOS) is an attractive target of cardiovascular gene therapy. The vascular prostheses, of which the inner surfaces are covered with mesenchymal stem cells (MSCs) overexpressing eNOS, are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. Herein, we attempted to develop small caliber vascular prostheses generating the bioactive proteins. Also, we attempted to transduce eNOS cDNA into MSCs. Methods and Results-The MSCs were isolated from rat bone marrow and transduced with each adenovirus harboring rat eNOS cDNA and ␤-galactosidase (␤-gal) (eNOS/MSCs and ␤-gal/MSCs). The ␤-gal/MSCs were impregnated into vascular prostheses, then the expressions of ␤-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl ␤-D-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of 3 H-arginine to 3 H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing ␤-gal. The amount of the 3 H-citrulline increased, and eNOS/MSCs were determined to generate enzymatic activity of eNOS. This activity was completely inhibited by N G -nitro-L-arginine methyl ester. Key Words: mesenchymal stem cells Ⅲ endothelial nitric oxide synthase Ⅲ gene-transduction Ⅲ adenovirus Ⅲ small caliber expanded polytetrafluoroethylene (ePTFE) vascular prosthesis I mpaired endothelial function induces several cardiovascular diseases, including atherosclerosis, hypertension, heart failure, arteriosclerosis obliterans, and coronary heart disease. Endothelial dysfunction also causes NO insufficiency, resulting in the limitation of NO-mediated signal transduction and excretion of bioactive hormone-like products. 1 The attenuated production of NO and the hormone-like products exaggerates these cardiovascular diseases further. Coronary artery disease is one of the most critical diseases enhanced by endothelial dysfunction, sometimes leading to irreversible myocardial damage. Some patients require repetitive coronary revascularization, including coronary artery bypass grafting, which may lead to a shortage of graft materials. Conclusions-TheSmall caliber vascular prostheses, which would be suitable for graft conduits for coronary artery bypass grafting or arteriosclerosis obliterans below the knee, have an extremely high failure rate that is attributed to thrombus formation and occlusion. Many attempts have been made to increase the patency of small-caliber vascular prostheses over the years. Recently, vascular grafts releasing NO infer possibilities preventing thrombosis and stenosis. 2,3 However, they are far from practical use, because the ma...

The aim of this study is to develop an experimental model of small caliber expanded polytetrafluoroethylene (ePTFE) vascular prostheses that produce recombinant proteins by seeding genetically modified bone marrow mesenchymal stem cells (MSC). Beta-galactosidase (beta-gal) cDNA was transduced into rat MSC mediated by an adenovirus vector. The cells were impregnated into the ePTFE vascular prostheses measuring 2 mm in internal diameter and 90 microm in fibril length, followed by 48 h of incubation. The expressions of beta-gal were determined by X-gal staining. The luminal surface of the ePTFE vascular prostheses was covered with the MSC expressing beta-gal. Most of the gene-transduced MSC spread along the fibers forming colonies. These results suggest that small caliber vascular prostheses, in which the inner surface was seeded by genetically modified MSC, produced recombinant proteins. This may be a preliminary model to autocrine functioning vascular prostheses.