Abstract:
An increasing number of models used to examine the role of particular signaling pathways in vasculature and the development of pulmonary hypertension (PH) are based on animals with different genetic modifications. The present study explores the severity of PH-related lesions that can be provided by a genetic particular model in accordance to the most common non-genetic PH inducers such as chronic exposure to hypoxia or single injection of monocrotaline. A review of 516 interventions on a variety of animal models was performed. It examined the advantages of various genetically-driven procedures intended to develop spontaneous PH, and the effects of combining such procedures with common PH models or other stimuli (\'second-hit\') with the aim of exacerbating pulmonary artery remodeling, right ventricle hypertrophy and hemodynamics or animal mortality. A wide range of genetically-modified rodents are used for pre-clinical studies on PH, with different response to the genetic modification as compared to the most common non-genetic stimuli. Nevertheless, they could highlight the mechanisms and pathways that contribute to the expression of pathophysiological features of the disease, and they could be helpful in the identification of additional targets for new drugs.
摘要:
用于检查特定信号传导途径在脉管系统中的作用和肺动脉高压(PH)发展的模型越来越多,这些模型基于具有不同遗传修饰的动物。本研究探讨了根据最常见的非遗传PH诱导剂,例如慢性暴露于缺氧或单次注射野百合碱,可通过遗传特定模型提供的PH相关病变的严重程度。对多种动物模型进行了516种干预措施的综述。它研究了旨在开发自发性PH的各种遗传驱动程序的优势,以及将此类程序与常见PH模型或其他刺激(“二次打击”)结合使用以加剧肺动脉重塑为目的的效果,右心室肥大和血流动力学或动物死亡率。广泛的转基因啮齿动物用于PH的临床前研究,与最常见的非遗传刺激相比,对遗传修饰的反应不同。然而,它们可以突出促进疾病病理生理特征表达的机制和途径,它们可能有助于识别新药的其他靶标。