Objective-Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium. Methods and Results-The human VEGF 165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, ␣-smooth muscle actin-positive cells were most increased in the VEGF group. Key Words: angiogenesis Ⅲ gene therapy Ⅲ myocardial infarction Ⅲ stem cell Ⅲ transplantation C ell transplantation has become a promising novel therapy for ischemic heart disease and heart failure. Recent studies have revealed that various types of cells are effective in cell transplantation after myocardial infarction (MI), such as skeletal myoblasts, 1,2 smooth muscle cells, 3 and bone marrow mononuclear cells. 4 Bone marrow mononuclear cells are especially useful because they contain, among various lineage cells, hematopoietic cells and endothelial progenitor cells; therefore they have the ability to induce angiogenesis in ischemic tissue. A reported clinical trial of cell transplantation with skeletal myoblasts and mononuclear bone marrow cells showed that such therapies can have cardioprotective and angiogenic effects after MI. 5,6 However, selection of the most appropriate cell types for transplantation is controversial. Conclusions-ThisMesenchymal stem cells (MSCs) are isolated from bone marrow mononuclear cells and can be expanded ex vivo. Under appropriate culture conditions, MSCs have the potential to terminally differentiate into osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes, hematopoietic supporting stroma, and endothelial cells. 7 MSCs have also been used in a model of cell transplantation, 8,9 showing that these cells could differentiate into myogenic cells. Therefore, MSCs have many characteristics that make them useful for cellular therapy.Vascular endothelial growth factor (VEGF) is a strong therapeutic reagent for treating ischemia by inducing angiogenesis. 10 It has been reported that direct intramyocardial gene transfer results in localized enhancement of VEGF levels and successful angiogenesis in animal models of MI. 11 Furthermore, recent h...

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Noninvasive measurement of CFR by TTDE provides data equivalent to those obtained by Tl-201-SPECT for physiologic estimation of the severity of LAD stenosis.

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p<0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p<90.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r=0.71) and inversely related to the ejection fraction (r= -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated. (Circulation 1990;81:156-163) R ecent studies in experimental models suggest that acute myocardial ischemia is associated with activation of the complement system. First, studies in the baboon have established that C3, C4, and C5 are deposited in most infarction myocardial fibers.12 Second, by inactivating the complement system in vivo with cobra venom factor, a significant reduction in myocardial damage was achieved in an animal model.3 Also, a few studies report the complement activation in vivo in patients with acute myocardial infarction (AMI).4-6 However, it is not clear whether the activated complement system affects the myocardial necrotic size and cardiac function in human myocardial infarction. It is also unknown whether or not the complement system is activated in patients with angina pectoris (AP). This study assessed complement activation in patients with AMI and AP by directly measuring by-products of the reaction. The degree of activation of the complement system was compared with the hemodynamic manifestations and peak creatine phosphokinase (CPK) in patients with AMI. MethodsThe study group consisted of 31 patients with AMI, 17 patients with unstable angina pectoris (UAP), 19 patients with stable angina pectoris (SAP), and 20 normal volunteers (Table 1). AMI was defined by at least two of the following: 1) angina lasting longer than 30 minutes, unrelieved by rest, 2) serum creatine kinase-MB fraction greater than 5%, 3) inversion or elev...