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1.
Proc Natl Acad Sci U S A ; 106(37): 15885-90, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19717420

RESUMO

Primitive cells capable of generating small resistance arterioles and capillary structures in the injured myocardium have been identified repeatedly. However, these cells do not form large conductive coronary arteries that would have important implications in the management of the ischemic heart. In the current study, we determined whether the human heart possesses a class of progenitor cells that regulates the growth of endothelial cells (ECs) and smooth muscle cells (SMCs) and vasculogenesis. The expression of vascular endothelial growth-factor receptor 2 (KDR) was used, together with the stem cell antigen c-kit, to isolate and expand a resident coronary vascular progenitor cell (VPC) from human myocardial samples. Structurally, vascular niches composed of c-kit-KDR-positive VPCs were identified within the walls of coronary vessels. The VPCs were connected by gap junctions to ECs, SMCs, and fibroblasts that operate as supporting cells. In vitro, VPCs were self-renewing and clonogenic and differentiated predominantly into ECs and SMCs and partly into cardiomyocytes. To establish the functional import of VPCs, a critical stenosis was created in immunosuppressed dogs, and tagged human VPCs were injected in proximity to the constricted artery. One month later, there was an increase in coronary blood flow (CBF) distal to the stenotic artery, resulting in functional improvement of the ischemic myocardium. Regenerated large, intermediate, and small human coronary arteries and capillaries were found. In conclusion, the human heart contains a pool of VPCs that can be implemented clinically to form functionally competent coronary vessels and improve CBF in patients with ischemic cardiomyopathy.


Assuntos
Células-Tronco Adultas/citologia , Vasos Coronários/citologia , Actinas/metabolismo , Células-Tronco Adultas/fisiologia , Células-Tronco Adultas/transplante , Animais , Diferenciação Celular , Proliferação de Células , Separação Celular , Conexina 43/metabolismo , Circulação Coronária , Estenose Coronária/patologia , Estenose Coronária/fisiopatologia , Estenose Coronária/terapia , Vasos Coronários/fisiopatologia , Cães , Células Endoteliais/citologia , Células Endoteliais/fisiologia , Perfilação da Expressão Gênica , Humanos , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/terapia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/fisiologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Regeneração/genética , Regeneração/fisiologia , Transplante Heterólogo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
2.
Int J Cardiol ; 128(3): 427-9, 2008 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-18396342

RESUMO

BACKGROUND: Given the frequent involvement of infra-popliteal arteries, an ipsilateral antegrade common femoral artery puncture (ACFAP) is usually preferred to a contralateral retrograde femoral access for percutaneous transluminal angioplasty (PTA) in patients with critical limb ischemia (CLI). Because of the frequent difficulty to get a sufficient manual pressure on the puncture site, ACFAP is burdened by a high number of bleeding local complications, including retroperitoneal haematoma. We report a series of patients who consecutively received a clip-based arterial closure device after ACFAP and ipsilateral PTA for CLI. METHODS: Thirty patients (73+/-6 years; 18 men; 100% diabetes) admitted to our hospital because of CLI consecutively underwent peripheral PTA after an ACFAP and received a clip-based arterial closure device. Time to haemostasis was defined as the interval elapsed between clip deployment and first observed haemostasis. All patients were mobilized after 6 h. Follow-up was 30 days. RESULTS: All patients were on double anti-platelet therapy. At the end of the procedure, Activation Clotting Time was 226+/-37 s. Procedural success in delivering the clip was 100%. Time to haemostasis was 21+/-19 s. No major local vascular complications and in particular no retroperitoneal bleeding were documented. All patients could be discharged within the following 3 days. No major complications were noted during a 30 days follow-up. CONCLUSIONS: The use of a clip-based arterial closure device after ACFAP for peripheral PTA in CLI seems to be safe and effective.


Assuntos
Artéria Femoral/patologia , Artéria Femoral/fisiologia , Hemostasia/fisiologia , Punções/instrumentação , Instrumentos Cirúrgicos , Idoso , Angioplastia com Balão/instrumentação , Angioplastia com Balão/métodos , Feminino , Humanos , Masculino , Doenças Vasculares Periféricas/patologia , Doenças Vasculares Periféricas/terapia , Punções/métodos
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