Avila Maria D, Morgan James P, Yan Xinhua
Department of Internal Medicine, Carney Hospital, Tufts University School of Medicine, Boston, MA 02124, USA.
J Biomed Biotechnol. 2011;2011:141039. doi: 10.1155/2011/141039. Epub 2011 Apr 27.
The actions of Angiotensin II have been implicated in many cardiovascular conditions. It is widely accepted that the cardiovascular effects of Angiotensin II are mediated by different subtypes of receptors: AT(1) and AT(2). These membrane-bound receptors share a part of their nucleic acid but seem to have different distribution and pathophysiological actions. AT(1) mediates most of the Angiotensin II actions since it is ubiquitously expressed in the cardiovascular system of the normal adult. Moreover AT(2) is highly expressed in the developing fetus but its expression in the cardiovascular system is low and declines after birth. However the expression of AT(2) appears to be modulated by pathological states such as hypertension, myocardial infarction or any pathology associated to tissue remodeling or inflammation. The specific role of this receptor is still unclear and different studies involving in vivo and in vitro experiments have shown conflicting data. It is essential to clarify the role of the AT(2) receptor in the different pathological states as it is a potential site for an effective therapeutic regimen that targets the Angiotensin II system. We will review the different genetically modified mouse models used to study the AT(2) receptor and its association with cardiac hypertrophy and heart failure.
血管紧张素II的作用与许多心血管疾病有关。人们普遍认为,血管紧张素II的心血管效应是由不同亚型的受体介导的:AT(1)和AT(2)。这些膜结合受体有部分核酸相同,但分布和病理生理作用似乎不同。AT(1)介导了血管紧张素II的大部分作用,因为它在正常成年人的心血管系统中普遍表达。此外,AT(2)在发育中的胎儿中高度表达,但其在心血管系统中的表达较低,出生后会下降。然而,AT(2)的表达似乎受到病理状态的调节,如高血压、心肌梗死或任何与组织重塑或炎症相关的病理状态。该受体的具体作用仍不清楚,涉及体内和体外实验的不同研究显示了相互矛盾的数据。阐明AT(2)受体在不同病理状态下的作用至关重要,因为它是针对血管紧张素II系统的有效治疗方案的潜在靶点。我们将综述用于研究AT(2)受体及其与心肌肥大和心力衰竭关联的不同基因改造小鼠模型。