Coronary endothelium expresses a pathologic gene pattern compared to aortic endothelium:: Correlation of asynchronous hemodynamics and pathology in vivo
Coronary endothelium expresses a pathologic gene pattern compared to aortic endothelium:: Correlation of asynchronous hemodynamics and pathology in vivo
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DOI：
10.1016/j.atherosclerosis.2006.05.042
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发表时间：
2007-05-01
期刊：
影响因子：
5.3
通讯作者：
Tarbell, John M.
中科院分区：
文献类型：
--
作者：
Dancu, Michael B.;Tarbell, John M.
冠状动脉是循环中最易患病的动脉，其特征在于独特的血液动力学特征，其中由血流诱导的壁剪切应力（WSS）和由压力驱动的周向应变（CS）在时间上是高度异相的（异步血液动力学）。为了研究异步血流动力学与体内病理学之间是否存在相关性，我们检测了雄性新西兰兔两个不同血流动力学区域的内皮细胞（EC）基因表达和核形态：（左前降支cLAD）和主动脉（主动脉弓内曲率、外曲率和直降主动脉）。正面成像显示EC核长度有很强的相似性：cLAD和主动脉中的宽度比和取向角。然而，实时RT-PCR显示，冠状动脉与所有主动脉区域相比，eNOS mRNA水平显著降低（> 5倍），而ET-1显示出相反的趋势（类似于2.5倍）。具有特征性异步血流动力学的冠状动脉显示促动脉粥样硬化eNOS和ET-1基因表达谱，而EC核形态与主动脉中的非致动脉粥样硬化区域没有差异。这项研究表明，异步血流动力学和促动脉粥样硬化基因表达模式之间的相关性，在体内诱导固有的血液循环的血流动力学。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Coronary arteries are the most disease prone arteries in the circulation and are characterized by unique hemodynamic features, wherein wall shear stress (WSS) induced by blood flow and circumferential strain (CS) driven by pressure are highly out-of-phase temporally (asynchronous hemodynamics). To investigate whether there is a correlation between asynchronous hemodynamics and pathology in vivo, we examined endothelial cell (EC) gene expression and nuclear morphology in two distinct hemodynamic regions of male New Zealand rabbits: coronary arteries (left anterior descending artery cLAD), and aorta (aortic arch inner curvature, outer curvature, and straight descending aorta).En face imaging showed strong similarities in EC nuclear length:width ratio and angle of orientation in the cLAD and aorta. Real-time RT-PCR, however, showed that coronary arteries had significantly reduced (> 5-fold) eNOS mRNA levels compared to all aortic regions, while ET-1 showed an opposite trend (similar to 2.5-fold). Coronary arteries with characteristic asynchronous hemodynamics displayed pro-atherogenic eNOS and ET-1 gene expression profiles while the EC nuclei morphology did not differ from non-atherogenic regions in the aorta. This study demonstrates a correlation between asynchronous hemodynamics and pro-atherogenic gene expression patterns in vivo that is induced by hemodynamics inherent to the circulation. (c) 2006 Elsevier Ireland Ltd. All rights reserved.