Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile.
Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile.
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DOI：
10.1016/j.jtcvs.2008.08.019
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发表时间：
2009-01
影响因子：
6
通讯作者：
Selzman, Craig H.
中科院分区：
文献类型：
--
作者：
Stansfield, William E.;Charles, Peter C.;Tang, Ru-Hang;Rojas, Mauricio;Bhati, Rajendra;Moss, Nancy C.;Patterson, Cam;Selzman, Craig H.
左心室肥大（LVH）是心血管疾病发病率和死亡率的一个非常普遍和可靠的预测因子。现有的研究已经非常详细的机制与它的发展，但这些发现的临床翻译仍然不能令人满意。我们提出了一种替代策略，重点是LVH回归的机制，而不是其进展，并假设LVH回归与不同的基因组谱相关。在C57 B16雄性小鼠中进行微创横向弓带和去带（或其各自的假手术）。左室肥厚的生理学评价采用经胸超声心动图，结构评价采用组织学，分子评价采用实时PCR。用Agilent小鼠44 k发育基因芯片对小鼠心脏进行基因组学分析。与对照组相比，捆绑28天的动物通过心脏重量/体重比、组织学、超声心动图和胎儿基因表达产生了强烈的肥大反应。这些参数在去条带后1周内逆转。LV组织的全基因组阵列显示288个基因在进展过程中差异表达，265个基因在消退过程中差异表达，只有23个基因在两个过程中共有。与LVH进展相关的结构相关模式相比，信号相关的表达模式在消退中更为普遍。此外，退行性心脏在能量代谢和蛋白质产生方面表现出相对更多的变化。这项研究证明了一个有效的模型来表征左室肥厚，并揭示了回归是基因组不同的发展。对这些表达谱的进一步研究将拓宽我们对LVH的理解，并提供一种新的治疗模式，专注于促进LVH的消退，而不仅仅是阻止其进展。
Left ventricular hypertrophy (LVH) is a highly prevalent and robust predictor of cardiovascular morbidity and mortality. Existing studies have finely detailed mechanisms involved with its development, yet clinical translation of these findings remains unsatisfactory. We propose an alternative strategy focusing on mechanisms of LVH regression rather than its progression and hypothesize that LVH regression is associated with a distinct genomic profile Minimally-invasive transverse arch banding and debanding (or their respective sham procedures) were performed in C57Bl6 male mice. LVH was assessed physiologically by transthoracic echocardiography, structurally by histology, and molecularly by real-time PCR. Mouse hearts were genomically analyzed with Agilent mouse 44k developmental gene chips. Compared to controls, animals banded for 28 days developed a robust hypertrophic response by heart weight/body weight ratio, histology, echocardiography, and fetal gene expression. These parameters were reversed within 1 week of debanding. Whole genome arrays on LV tissue revealed 288 genes differentially expressed during progression, 265 genes differentially expressed with regression, and only 23 genes shared by both processes. Signaling-related expression patterns were more prevalent with regression rather than the structural-related patterns associated with LVH progression. In addition, regressed hearts showed comparatively more changes in energy metabolism and protein production. This study demonstrates an effective model for characterizing LVH and reveals that regression is genomically distinct from its development. Further examination of these expression profiles will broaden our understanding of LVH and provide a novel therapeutic paradigm focused on promoting regression of LVH, not just halting its progression.
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影响因子：
4.6
作者：
Kunadian, Babu;Vijayalakshmi, Kunadian;Dunning, Joel
通讯作者：
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DOI：
10.1152/ajpheart.00196.2007
发表时间：
2008-02-01
影响因子：
4.8
作者：
Stansfield, William E.;Tang, Ru-Hang;Selzman, Craig H.
通讯作者：
Selzman, Craig H.
影响因子：
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作者：
Lecker, SH;Jagoe, RT;Goldberg, AL
通讯作者：
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影响因子：
5.8
作者：
Barry, WT;Nobel, AB;Wright, FA
通讯作者：
Wright, FA
DOI：
10.1152/ajpheart.00836.2004
发表时间：
2005-06-01
影响因子：
4.8
作者：
Gao, XM;Kiriazis, H;Du, XJ
通讯作者：
Du, XJ