RESUMO
BACKGROUND: Cardiovascular disease (CVD) remains a major cause of morbidity and mortality, especially in the presence of diabetes, possibly because of endothelial damage. Increased circulating progenitor cells (CPCs) and increased plasma markers of angiogenesis [vascular endothelial growth factor (VEGF) and the angiopoietins (Ang-1 and -2)] may be evidence of this damage. Treatment with hydroxy-methyl-glutaryl (HMG-CoA) reductase inhibitors ('statins') improves outcomes in patients with vascular disease, including diabetic patients. We hypothesized that 80 mg per day atorvastatin influences CPC counts of VEGF and the angiopoietins in patients with atherosclerotic CVD with or without diabetes mellitus. METHODS: Cardiovascular disease patients with diabetes mellitus (Group A, n = 14) and nondiabetic patients with CVD only (Group B, n = 10) took atorvastatin 80 mg per day for a period of 8-10 weeks. CPCs (CD34+/CD133+/CD45-) were defined by flow cytometry, plasma levels VEGF and Ang-1 and Ang-2 by ELISA). RESULTS: Circulating progenitor cell counts increased (P < 0.001) in Group A compared with a nonsignificant change in Group B (P = 0.37). VEGF levels fell significantly in Group A (P = 0.04) but no significant change was seen in Group B (P = 0.16). Whilst Ang-1 remained unchanged (P = 0.41), Ang-2 levels increased markedly in both groups (P < 0.05). These effects were independent of LDL and total cholesterol changes but were associated with HDL changes. CONCLUSION: High-dose atorvastatin increased circulating CPCs, reduced VEGF and increased Ang-2 in patients with diabetes and CVD, providing another possible pathophysiological mechanism for the beneficial effects of statins in CVD.
Assuntos
Antígenos CD/sangue , Aterosclerose/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirróis/uso terapêutico , Células-Tronco , Idoso , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Antígenos CD34/sangue , Aterosclerose/sangue , Aterosclerose/patologia , Atorvastatina , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Feminino , Humanos , Antígenos Comuns de Leucócito/sangue , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/sangue , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular/metabolismoAssuntos
Contagem de Células/normas , Química Clínica/normas , Células Endoteliais/citologia , Veias Umbilicais/citologia , Antígenos CD34/biossíntese , Antígeno CD146/biossíntese , Contagem de Células/métodos , Endotélio Vascular/citologia , Citometria de Fluxo , Humanos , Separação Imunomagnética , Fenótipo , Sensibilidade e EspecificidadeAssuntos
Neoplasias da Mama/etiologia , Diuréticos/efeitos adversos , Hipertensão/complicações , Inquéritos e Questionários , Fatores Etários , Idoso , Diuréticos/administração & dosagem , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Cancer, a proliferative disease hallmarked by abnormal cell growth and spread, is largely dependent on tumor neoangiogenesis, with evidence of vascular endothelial dysfunction. Novel ways to assess vascular function in cancer include measuring levels of circulating endothelial cells (CEC). Rare in healthy individuals, increased CEC in peripheral blood reflects significant vascular damage and dysfunction. They have been documented in many human diseases, including different types of cancers. An additional circulating cell population are endothelial progenitor cells (EPC), which have the ability to form endothelial colonies in vitro and may contribute toward vasculogenesis. At present, there is great interest in evaluating the role of EPC as novel markers for tumor angiogenesis and drug therapy monitoring. Recently, exocytic procoagulant endothelial microparticles (EMP) have also been identified. CEC, EPC, and EMP research works may have important clinical implications but are often impeded by methodological issues and a lack of consensus on phenotypic identification of these cells and particles. This review aims to collate existing literature and provide an overview on the current position of CEC, EPC, and EMP in cell biology terms and to identify their significance to clinical medicine, with particular emphasis on relationship with cancer.
Assuntos
Células Endoteliais/fisiologia , Endotélio Vascular/fisiopatologia , Neoplasias/patologia , Células-Tronco/fisiologia , Apoptose , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Medula Óssea/patologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , Humanos , Necrose , Células-Tronco/patologiaAssuntos
Extravasamento de Materiais Terapêuticos e Diagnósticos/complicações , Salvamento de Membro , Braço/patologia , Desbridamento , Extravasamento de Materiais Terapêuticos e Diagnósticos/patologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/terapia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Necrose , Pressão , Transplante de PeleAssuntos
Células Endoteliais/patologia , Hipertensão/fisiopatologia , Células-Tronco/patologia , Envelhecimento/fisiologia , Antígenos CD34/análise , Vasos Sanguíneos/química , Vasos Sanguíneos/patologia , Células Endoteliais/química , Humanos , Hipertensão/metabolismo , Hipertensão/patologia , Células-Tronco/químicaRESUMO
Circulating endothelial cells (CEC) have evolved as a novel method of assessing endothelial function. Rarely found in the peripheral blood of healthy individuals, CECs increase in a wide variety of conditions such as cardiovascular disease, cancer, infection and inflammatory states. Unlike immature endothelial progenitor cells (EPC), which are bone marrow derived, CECs are felt to represent the detachment of mature endothelial cells from the endothelial monolayer, as a result of endothelial insult. In this article we present an overview of CECs and their association with a broad spectrum of disease processes.