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与内皮祖细胞的纯度、生物学功能和激活潜能相关的因素。

Factors associated with purity, biological function, and activation potential of endothelial colony-forming cells.

机构信息

Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Keelung, Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R586-94. doi: 10.1152/ajpregu.00450.2010. Epub 2010 Dec 15.

Abstract

Endothelial colony-forming cells (ECFCs) are undergoing extensive investigations to tackle certain deliberating cardiovascular diseases. However, the success of this approach depends on a thorough understanding of ECFC biology. This study sought to determine the factors associated with the purity, biological function, and activation potential of ex vivo expanded ECFCs. Seventy-three patients with newly diagnosed coronary artery disease (CAD) and 24 controls were studied. ECFCs were cultured for up to 10 passages to investigate changes in and the impact of coronary risk factors on ECFC biological functions and the atherogenic potential. Passages 3-5 of ECFCs exhibited higher endothelial phenotype expression and better biological functions, in terms of nitric oxide secretion and tubular formation, but lower activation potentials compared with later passages (P <0.05). Studies on passage 3 showed that endothelial phenotype expression and biological functions were impaired, and the activation potentials of the ECFCs were significantly upregulated in subjects with coronary risk factors and especially those with CAD (P < 0.05). Furthermore, ECFCs were already activated before inflammatory stimulation in subjects with diabetes mellitus, hypertension, and CAD. Atorvastatin upregulated the endothelial nitric oxide synthase expression of ECFCs in CAD patients (P < 0.01), although not up to the baseline level of controls. In conclusion, the passage number and a variety of coronary risk factors were associated with the purity, biological function, and activation potential of ex vivo-expanded ECFCs. Functional assessments and manipulations of ECFCs have to be pursued in patients with extensive risk factors.

摘要

内皮祖细胞(ECFCs)正在进行广泛的研究,以解决某些心血管疾病。然而,这种方法的成功取决于对 ECFC 生物学的深入了解。本研究旨在确定与体外扩增 ECFC 的纯度、生物学功能和激活潜能相关的因素。研究了 73 例新发冠状动脉疾病(CAD)患者和 24 例对照者。培养 ECFC 多达 10 代,以研究冠状动脉危险因素对 ECFC 生物学功能和动脉粥样硬化潜能的变化和影响。第 3-5 代 ECFC 表现出更高的内皮表型表达和更好的生物学功能,表现在一氧化氮分泌和管状形成方面,但与后期代相比激活潜能较低(P<0.05)。第 3 代研究显示,内皮表型表达和生物学功能受损,且具有冠状动脉危险因素的患者,尤其是 CAD 患者的 ECFC 激活潜能显著上调(P<0.05)。此外,在患有糖尿病、高血压和 CAD 的患者中,ECFC 甚至在炎症刺激前就已经被激活。阿托伐他汀可上调 CAD 患者 ECFC 的内皮型一氧化氮合酶表达(P<0.01),尽管未达到对照组的基线水平。总之,代次和多种冠状动脉危险因素与体外扩增的 ECFC 的纯度、生物学功能和激活潜能相关。在具有广泛危险因素的患者中,必须对 ECFC 的功能评估和操作进行研究。

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