Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats: rationale for targeting the β-adrenergic and renin-angiotensin systems
Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats: rationale for targeting the β-adrenergic and renin-angiotensin systems
复制标题
DOI：
10.1152/ajpheart.01046.2008
复制
发表时间：
2009-03-01
影响因子：
4.8
通讯作者：
Arsenault, Marie
中科院分区：
文献类型：
--
作者：
Champetier, Serge;Bojmehrani, Azadeh;Arsenault, Marie
作者S、博伊梅赫拉尼·A、博阿多因·J、兰昌斯·D、普兰特·E、鲁塞尔·E、库埃特·J、阿森诺·M。主动脉瓣关闭不全大鼠左室向心性肥厚的基因图谱：以β-肾上腺素能和肾素-血管紧张素系统为靶点的理论基础。Am J Physiol心脏圈Physiol 296：H669-H677,2009。2008年12月26日首次出版；DOI：10.1152/ajpheart.01046.2008。-主动脉瓣返流(AR)对左心室(LV)施加严重的容量超负荷，导致扩张、离心性肥厚，并最终失去功能。AR对LV基因表达的影响知之甚少。因此，我们在急性和严重变应性鼻炎大鼠的左室进行了基因表达谱研究。2周后，在21,910个基因中，我们发现了特异上调的基因和29个下调的基因。在上调的基因中，有很大比例与细胞外基质有关。我们随后通过定量RT-PCR(qRT-PCR)研究了19个基因的子集，以了解在2周后左室中看到的调制是否在慢性期(6和12个月后)持续存在，并发现它确实持续。在我们的动物模型中，肾上腺素能系统和肾素-血管紧张素系统被过度激活，我们很感兴趣地观察使用美托洛尔(25 mg·kg(-1)·day(-1))和卡托普利(100 mg·kg(-1).day(-1))阻断这些系统是否会在6个月后改变AR大鼠一些上调的LV基因的表达。通过qRT-PCR，我们观察到该药可完全或部分逆转I型和III型前胶原、纤维连接蛋白、心钠素、转化生长因子-β(2)和结缔组织生长因子的LV基因表达水平的上调。这些观察结果为在AR的医学治疗中针对这些系统的医学策略提供了分子基础，并扩展了这种形式的LV容量超载的研究范式。
Champetier S, Bojmehrani A, Beaudoin J, Lachance D, Plante E, Roussel E, Couet J, Arsenault M. Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats: rationale for targeting the beta-adrenergic and renin-angiotensin systems. Am J Physiol Heart Circ Physiol 296: H669-H677, 2009. First published December 26, 2008; doi:10.1152/ajpheart.01046.2008.-Aorticvalve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV), which results in dilation, eccentric hypertrophy, and eventually loss of function. Little is known about the impact of AR on LV gene expression. We, therefore, conducted a gene expression profiling study in the LV of rats with acute and severe AR. We identified 64 genes that were specifically upregulated and 29 that were downregulated out of 21,910 genes after 2 wk. Of the upregulated genes, a good proportion was related to the extracellular matrix. We subsequently studied a subset of 19 genes by quantitative RT-PCR (qRT-PCR) to see if the modulation seen in the LV after 2 wk persisted in the chronic phase (after 6 and 12 mo) and found that it did persist. Knowing that the adrenergic and renin-angiotensin systems are overactivated in our animal model, we were interested to see if blocking those systems using metoprolol (25 mg.kg(-1).day(-1)) and captopril (100 mg.kg(-1).day(-1)) would alter the expression of some upregulated LV genes in AR rats after 6 mo. By qRT-PCR, we observed that upregulations of LV mRNA levels encoding for procollagens type I and III, fibronectin, atrial natriuretic peptide, transforming growth factor-beta(2), and connective tissue growth factor were totally or partially reversed by this treatment. These observations provide a molecular rationale for a medical strategy aiming these systems in the medical treatment of AR and expand the paradigm in the study of this form of LV volume overload.