[Left ventriculoplasty in a patient with suspected takotsubo cardiomyopathy followed by a left ventricular aneurysm].

A 42-year-old woman was admitted with chest pain. Coronary angiography did not reveal any significant stenosis, but left ventriculography showed akinesis and ballooning of the apex with a hyperkinetic basal segment indicating Takotsubo cardiomyopathy. Cerebral embolism occurred after one and a half years because of a left ventricular thrombus. The apical akinesis had worsened to a left ventricular aneurysm (maximum diameter 43 mm). The left ventricle was reconstructed to avoid repeated thrombus formation and cerebral infarction despite anticoagulant therapy. A pathological assessment revealed a fibrotic myocardium, but the cause of the cardiac aneurysm remained unknown. Although the outcome of Takotsubo cardiomyopathy is relatively good, careful observation and appropriate treatment are needed considering the possibility of aggravation.

Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension.

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. CONCLUSIONS: Intravenous implantation of MSCs/eNOS may offer ameliorating effects on PH-related RV impairment and survival time.

Synthetic vascular prosthesis impregnated with mesenchymal stem cells overexpressing endothelial nitric oxide synthase.

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 beta-galactosidase (beta-gal) (eNOS/MSCs and beta-gal/MSCs). The beta-gal/MSCs were impregnated into vascular prostheses, then the expressions of beta-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of 3H-arginine to 3H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing beta-gal. The amount of the 3H-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. CONCLUSIONS: The inner surface of expanded polytetrafluoroethylene vascular prostheses seeded with lacZ gene-transduced MSCs exhibited recombinant proteins. Development of eNOS/MSC-seeded vascular prostheses would promise much longer graft patency and vasculoprotective effects.

Synthetic vascular prosthesis impregnated with genetically modified bone marrow cells produced recombinant proteins.

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.