These data suggest that patients with acute type B dissection who have a large aortic diameter (> or = 40 mm) and a patent primary entry site in the thorax should be treated surgically during the acute phase on the condition that the surgical risk in this phase is limited.

Intravascular stents have proved useful as angioplasty devices, but intimal hyperplasia after stent implantation remains an unsolved problem. In the present study, we analyzed the spatial and chronological distribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after stent implantation (Gianturco's Z type) by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (SMI, SM2, and SMemb). Stent implantation induced regional injury in the arterial wall. Medial SMCs then began to proliferate adjacent to the injured SMCs, maximally on day 4 (PCNA index in the media: 3.9±3.4%[mean±SD]), and were modulated to the embryonic phenotype (SMemb-positive and SM2-negative). They migrated into I ntravascular stents have been extensively investigated as tools of angioplasty and proved useful in elastic recoil, restenosis, and dissection after balloon angioplasty.1 They have also been applied to various sites of stenotic lesions, including coronary arteries.1 -4 Several clinical trials have demonstrated that intracoronary stenting may be more effective than percutaneous transluminal coronary angioplasty (PTCA) in maintaining long-term vessel patency and may reduce the incidence of restenosis after angioplasty. "9 Such reduction in the restenosis rate is considered to be due to a larger acute gain obtained by stent implantation, although late loss of diameter is greater after stenting than that after PTCA. 7 9 Thus, restenosis after stenting still remains an unsolved problem.Pathological specimens of restenotic lesions after stenting show intimal hyperplasia, composed of abundant smooth muscle cells (SMCs) mixed with various degrees of connective tissue matrix. This study was presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.Reprint requests to Hikaru Matsuda, MD, First Department of Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.© 1994 American Heart Association, Inc.the intima and proliferated most frequently on day 7 (PCNA index in the intima: 20.3±5.5%) and subsequently led to fibrocellular neointima formation at 2 weeks and later. At 1 month after implantation and later, SMC proliferation was rare, and the phenotype of intimal SMCs was gradually returning to the adult type (SMemb-negative and SM2-positive). Thus, this stent implantation model demonstrates that the regional effect on arterial wall by stenting leads to neointima formation through transient and regional proliferation and migration of SMCs and their phenotypic modulations.

The neointima in the vein graft was formed initially by means of migration and proliferation of the phenotypically modulated, dedifferentiated-type SMCs and continued to thicken by means of sustained ECM accumulation, including type I collagen and decorin, in association with the prolonged presence of the dedifferentiated-type SMCs. These chronologic features in cell kinetics and ECM accumulation may contribute to the frequent occurrence of graft wall thickening that occurs in the vein grafts.

The donor hearts were transfected with F-ODN and beta-gal gene in almost all layers of the myocardium as a result of coronary infusion of the HVJ liposome during cardioplegic arrest. Our method is seen as a novel in vivo gene transfer technique for the heart and may provide a new tool for both research and therapy of heart transplantation.

The senescent cell-derived inhibitor (sdi)-1 (p21) protein heavy isoforms, adult type specific SM2 and embryonic has been identified as a downstream mediator of the tumor specific SMemb/NMHC-B, demonstrated expression of the suppressor p53 in the cell cycle regulation. In this study, adult phenotype of VSMCs in the neointima of sdi-1 genewe focused on the function of sdi-1 gene in inhibiting vastransfected vein grafts at 2 weeks after the operation, while cular smooth muscle cell (VSMC) proliferation after vein the neointima was predominantly composed of embryonic grafting in a rabbit model. To test the hypothesis, we transphenotype of VSMCs in the control grafts. Overall, these fected human sdi-1 gene by an intra-operative approach.results demonstrate that a single intraluminal incubation of Accompanied by markedly increased sdi-1 protein, the sighuman sdi-1 gene can result in a significant inhibition of nificant increase in PCNA-stained VSMCs in vein grafts neointimal formation after vein grafting, associated with was inhibited by transfection of sdi-1 gene. Moreover, at 2 phenotypic change of VSMCs from neonatal to adult type weeks after transfection, transfer of sdi-1 gene resulted in in a rabbit model. Inhibition of hyperplasia in a graft model a significant inhibition in neointimal formation, compared by transfection of sdi-1 gene may be due to the change in with control vector. Of importance, immunohistological VSMC phenotype from neonatal to adult, in addition to the studies determining the expression pattern of myosin inhibition of VSMC growth.

No abstract

Our objective was to define the signaling mechanisms by which mitogens such as insulin-like growth factor-I (IGF-I) regulate vascular smooth muscle cell (VSMC) apoptosis. We confirmed that IGF-I inhibits serum withdrawal-induced apoptosis of cultured VSMCs in a dose-dependent and time-dependent fashion. To test the hypothesis that the phosphatidylinositol (PI) 3-kinase signaling pathway regulates VSMC survival, we examined the relationship between PI 3-kinase activity and cell fate. PI 3-kinase was elevated in viable VSMCs maintained in serum-containing medium, declined significantly in response to serum withdrawal, and increased in response to IGF-I-induced survival. Moreover, blockade of PI 3-kinase with 2 structurally dissimilar inhibitors (wortmannin or LY294002) abolished the capacity of IGF-I to maintain VSMC viability. Similarly, transient transfection of a dominant-negative Deltap85 PI 3-kinase mutant construct abrogated the capacity of IGF-I to prevent VSMC death. Thus, PI 3-kinase is a critical antiapoptotic signal in VSMCs. To define the distal element of the antiapoptotic cascade, we tested the hypothesis that IGF-I inhibits the influence of the proapoptotic gene Bad. Indeed, IGF-I stimulates increased expression of the inactive, phosphorylated form of Bad by a PI 3-kinase-dependent pathway. Moreover, the proapoptotic effect of Bad was attenuated by the stimulation of IGF-I. Thus, growth factors appear to prevent VSMC death by activating signal transduction pathways linked to apoptotic regulatory genes.

We believe that this method represents a novel in vivo gene transfer technique for the heart and thus may provide a new tool for research and therapy of heart transplantation.