RESUMO
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used to decrease cholesterol synthesis and are well established to reduce vascular diseases. Recently, it has been proposed that statins mobilize endothelial progenitor cells from bone marrow during the first four weeks, which could help to prevent vascular diseases. However, in humans there are few data concerning the long term effects of statin treatment on these endothelial progenitor cells. We investigated whether endothelial progenitor cells can be detected and characterized in patients receiving long term statin therapy. Mononuclear cells from patients receiving or not receiving statin therapy were assessed for progenitor cell content by flow cytometry and were cultured in specific conditions to determine the number and the type of progenitors. Our results showed there were significantly more CD34(+), CD34(+)/CD144(+) circulating progenitor cells in the statin(pos) group than in the statin(neg) group. In culture two types of endothelial progenitor cells were detected. Early endothelial progenitor cells gave colonies at day 5 comprising elongated cells whereas late endothelial progenitor cells generated cobblestone-like colonies with strong proliferation capacities. The number of circulating early endothelial progenitor cells was significantly higher in the statin(neg) group, while only late endothelial progenitor cells were detected in the statin(pos) group. Moreover, cells from cobblestones clearly had an endothelial phenotype CD31(+), VEGF-R2(+), CD34(+), CD146(+) in contrast to cells from colonies from early endothelial progenitor cells, which were VEGF-R2(low), CD34(-). These results strongly suggest that long term statin treatment specifically maintains late endothelial progenitor cells in circulation with a CD34(+)/CD144(+) phenotype.
Assuntos
Doença das Coronárias/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Células-Tronco/efeitos dos fármacos , Idoso , Antígenos CD/sangue , Antígenos CD34/sangue , Antígeno CD146/sangue , Caderinas/sangue , Contagem de Células , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Doença das Coronárias/sangue , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Células-Tronco/citologia , Células-Tronco/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: Cellular cardiomyoplasty is a promising approach to improve postinfarcted cardiac function. The differentiation pathways of engrafted mesenchymal progenitor cells (MPCs) and their effects on the left ventricular function in a rat myocardial infarct heart model were analyzed. METHODS AND RESULTS: A ligation model of left coronary artery of Lewis rats was used. MPCs were isolated by bone marrow cell adherence. Seven days after ligation, MPCs labeled with 4',6-diamidino-2'-phenylindole were injected into the infarcted myocardium (n=8). Culture medium was injected in the infarcted myocardium of control animals (n=8). Thirty days after implantation, immunofluorescence studies revealed some engrafted cells expressing a smooth muscle phenotype (alpha SM actin+), as similarly observed in culture. Other engrafted cells lost their smooth muscle phenotype and acquired an endothelial phenotype (CD31+). Furthermore, vessel density was augmented in the MPC group in comparison with the control group. After 30 days, echocardiography showed an improvement on left ventricular performance in the MPCs compared with the control group. CONCLUSIONS: In vivo administration of syngenic MPCs into a rat model of myocardial infarcted heart was safety demonstrated. Some engrafted cells appeared to differentiate into endothelial cells and loss their smooth muscle phenotype. MPC engraftment might to contribute to the improvement on the cardiac function in such a setting.
Assuntos
Endotélio Vascular/citologia , Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Células Cultivadas , Vasos Coronários/patologia , Masculino , Mesoderma/citologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Fenótipo , Ratos , Ratos Endogâmicos Lew , Células-Tronco/citologia , Células-Tronco/fisiologia , Ultrassonografia , Função Ventricular EsquerdaAssuntos
Antineoplásicos Fitogênicos/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Paclitaxel/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Evolução Fatal , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Choque Cardiogênico/etiologiaRESUMO
BACKGROUND: From a registry of 249 confirmed pulmonary embolism (PE) patients submitted to thrombolytic therapy (TT), we analysed predictors of in-hospital course and long-term mortality. METHODS AND RESULTS: The combined clinical end point of in-hospital course associated death, recurrent PE, repeat thrombolysis, surgical embolectomy or bleeding complications. The long-term follow-up included analysis of survival, and occurrence of PE-related events, defined as recurrent deep vein thrombosis, recurrent PE, occurrence of congestive heart failure or change of New York Heart Association functional class to class III or IV in patients who survived the acute phase.In-hospital clinical course was uneventful in 165 (66.3%) patients. Initial right ventricular (RV) dysfunction was reversible in 80% within 48 h following TT. Initial pulmonary vascular obstruction >70% (RR=5.3 [2.1; 13.6]); haemodynamic instability at presentation (RR=2.6 [1.1; 6]); persistence of septal paradoxical motion after TT (RR=5.9 [1.4; 25.9]); and insertion of intracaval filter (RR=3.7 [1.4; 9.4]) were independent predictors of poor in-hospital course. Mean follow-up was 5.3+/-2.6 years. Of the 227 patients alive after the hospital stay, the probability of survival was 92% at 1 year, 79% at 3 years and 56% at 10 years. Multivariate predictors of long-term mortality were age >75 years (RR=2.73 [2.18; 3.21]; P=0.0002), persistence of vascular pulmonary obstruction >30% after thrombolytic treatment (RR=2.22 [1.69; 2.74]; P=0.003), and cancer (RR=2.03 [1.40; 2.65]; P=0.04). CONCLUSION: The recovery of RV function should be considered as a marker of thrombolysis efficacy, while residual pulmonary vascular obstruction and cancer are independent predictors of long-term mortality. These results advocate the identification of high-risk patients by means of systematic lung-scan and echocardiography pre- and post-thrombolysis, and raise the question of the need for thromboendarterectomy in patients with residual pulmonary vascular obstruction.