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首页> 外文期刊>American Journal of Physiology >Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention.
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Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention.

机译：冠状动脉内施用FGF-2：心肌沉积和deposition留的计算模型。

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This study uses a computational model to characterize the myocardial deposition and retention of basic fibroblast growth factor (FGF-2) at the cellular level after intracoronary (IC) administration of exogenous FGF-2. The model is applied to the in situ conditions present within the myocardium of a dog for which the plasma pharmacokinetics resulting from IC injection of FGF-2 were recorded. Our estimates show that the processes involved in FGF-2 signaling are not diffusion limited; rather, the response time is determined by the reaction time of FGF-2 binding to cell surface receptors. Additionally, the processes of receptor secretion and internalization are found to play crucial roles in the FGF-2 dynamics; future experiments are required to quantify these processes. The model predictions obtained in this study suggest that IC administration of FGF-2 via either a single bolus or repetitive injections causes a transient increase (time scale of hours) in myocardial FGF-2 concentration if the endogenous level of free interstitial FGF-2 is low enough to allow permeation of FGF-2 molecules from the microvascular to the interstitial spaces. The model shows that the majority (64%) of the extracellular FGF-2 ligands are located within the interstitium, and similar fractions are found in the basement membrane and extracellular matrix. Among the FGF-2 molecules found within the interstitium, 2% are free and 98% are bound to interstitial heparan sulfate proteoglycans. These results support the theory of extracellular control of the bioavailability of FGF-2 via dynamic storage of FGF-2 within the basement membrane and extracellular matrix.
机译：这项研究使用计算机模型在冠状动脉内（IC）给予外源性FGF-2后，在细胞水平上表征了碱性成纤维细胞生长因子（FGF-2）的心肌沉积和保留。将该模型应用于犬心肌内存在的原位条件，并记录了由IC-2注射FGF-2导致的血浆药代动力学。我们的估计表明，FGF-2信号传导所涉及的过程不受扩散的限制。相反，响应时间取决于FGF-2与细胞表面受体结合的反应时间。另外，发现受体分泌和内在化的过程在FGF-2动力学中起关键作用。需要未来的实验来量化这些过程。在这项研究中获得的模型预测表明，如果游离间质FGF-2的内源性水平为IA，通过单次推注或重复注射进行FGF-2的IC给药会导致心肌FGF-2浓度瞬时增加（小时刻度）。足够低，以允许FGF-2分子从微血管渗透到间隙。该模型显示，大多数（64％）细胞外FGF-2配体位于间质内，并且在基底膜和细胞外基质中也发现了相似的部分。在间质中发现的FGF-2分子中，有2％是游离的，有98％与间质硫酸乙酰肝素蛋白聚糖结合。这些结果支持通过FGF-2在基膜和细胞外基质内的动态储存来对FGF-2的生物利用度进行细胞外控制的理论。

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