Vasquez Alejandro, Atallah-Yunes Nader, Smith Frank C, You Xiaomang, Chase Sharon E, Silverstone Allen E, Vikstrom Karen L
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Cardiovasc Toxicol. 2003;3(2):153-63. doi: 10.1385/ct:3:2:153.
The aryl hydrocarbon receptor (AhR), a ligand activated transcription factor, is the receptor for the polycyclic aromatic hydrocarbons found in tobacco smoke, polychlorinated biphenyls, and the environmental pollutant, dioxin. To better understand the role of the AhR in the heart, echocardiography, invasive measurements of aortic and left ventricular pressures, isolated working heart preparations, as well as morphological and molecular analysis were used to investigate the impact of AhR inactivation on the mouse heart using the AhR knockout as a model. Cardiac hypertrophy is an early phenotypic manifestation of the AhR knockout. Although the knockout animals were not hypertensive at the ages examined, cardiomyopathy accompanied by diminished cardiac output developed. Despite the structural left ventricular remodeling, the hearts of these animals exhibit minimal fibrosis and do not have the expected increases in surrogate molecular markers of cardiac hypertrophy. The anatomic remodeling without typical features of molecular remodeling is not consistent with hypertrophic growth secondary to pressure or volume overload, suggesting that increased cardiomyocyte size may be a direct consequence of the absence of the AhR in this cell type.
芳烃受体（AhR）是一种配体激活的转录因子，是烟草烟雾中发现的多环芳烃、多氯联苯和环境污染物二恶英的受体。为了更好地了解AhR在心脏中的作用，利用AhR基因敲除小鼠作为模型，通过超声心动图、主动脉和左心室压力的侵入性测量、离体工作心脏标本以及形态学和分子分析来研究AhR失活对小鼠心脏的影响。心脏肥大是AhR基因敲除的早期表型表现。尽管在所检查的年龄，基因敲除动物没有高血压，但出现了伴有心输出量减少的心肌病。尽管左心室发生了结构性重塑，但这些动物的心脏表现出最小程度的纤维化，并且心脏肥大的替代分子标志物没有预期的增加。没有典型分子重塑特征的解剖学重塑与压力或容量超负荷继发的肥厚性生长不一致，这表明心肌细胞大小增加可能是这种细胞类型中缺乏AhR的直接后果。
