A process-based review of mouse models of pulmonary hypertension.
A process-based review of mouse models of pulmonary hypertension.
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DOI：
10.4103/2045-8932.105030
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发表时间：
2012-10
影响因子：
2.6
通讯作者：
West J
中科院分区：
文献类型：
--
作者：
Das M;Fessel J;Tang H;West J
转基因小鼠模型具有无与伦比的能力来确定涉及各类人类肺动脉高压（PH）的分子和生理病因学的不同过程背后的机制。已知与 PH 相关的过程（有大量可用的小鼠模型）包括：（1）通过分泌的血管活性因子调节血管张力； (2)通过钾、钙通道调节血管张力； (3) 通过改变代谢过程（通过改变底物使用或通过循环因子）来调节血管重塑； (4)肺动脉压升高之前或之后的自发血管重塑； (5) 张力和重塑主要由炎症驱动的模型。与人类疾病相比，小鼠 PH 的发展必然更快，并且具有不同的生理后果，因此小鼠无法成为 PH 自然史的模型。然而，转基因小鼠模型是研究肺血管功能和疾病过程的完美工具，并且可以有效地用于测试针对疾病所涉及的特定分子途径和过程设计的干预措施。
Genetically modified mouse models have unparalleled power to determine the mechanisms behind different processes involved in the molecular and physiologic etiology of various classes of human pulmonary hypertension (PH). Processes known to be involved in PH for which there are extensive mouse models available include the following: (1) Regulation of vascular tone through secreted vasoactive factors; (2) regulation of vascular tone through potassium and calcium channels; (3) regulation of vascular remodeling through alteration in metabolic processes, either through alteration in substrate usage or through circulating factors; (4) spontaneous vascular remodeling either before or after development of elevated pulmonary pressures; and (5) models in which changes in tone and remodeling are primarily driven by inflammation. PH development in mice is of necessity faster and with different physiologic ramifications than found in human disease, and so mice make poor models of natural history of PH. However, transgenic mouse models are a perfect tool for studying the processes involved in pulmonary vascular function and disease, and can effectively be used to test interventions designed against particular molecular pathways and processes involved in disease.