期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 2, 期 2, 页码 116-U72出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.108.806935
关键词
heart; hypertrophy; gene expression; self-organizing map; GEDI; time warp
资金
- Harvard University
- National Institutes of Health [HL079126-01A2]
Background-Cardiac hypertrophy is classically regarded as a compensatory response, yet the active tissue remodeling processes triggered by various types of mechanical stress can enhance or diminish the function of the heart. Despite the disparity in outcomes, there are similarities in the hypertrophic responses. We hypothesized that a generic genetic response that is not dependent on the particular nature of the hypertrophic stimulus exists. To test our hypothesis, we compared the temporal evolution of transcriptomes measured in hearts subjected to either adaptive (exercise-induced) or maladaptive (aortic banding-induced) hypertrophy. Methods and Results-Generic hypertrophy-associated genes were identified and distinguished from stimulus-dependent transcripts by coupling a metric of cardiac growth with a dynamic time-warping algorithm to align transcriptome changes with respect to the hypertrophy response. The major differences in expression between the adaptive and maladaptive hypertrophy models were centered around the genes involved in metabolism, fibrosis, and immune response. Conversely, transcripts with common expression patterns in both hypertrophy models were associated with signal transduction, cytoskeletal development, and muscle contraction. Thus, despite the apparent differences in the expression response of the heart to either athletic conditioning or pressure overload, there is a set of genes that displays similar expression profiles. Conclusions-This finding lends support to the notion of a generalized cardiac growth mechanism that is activated in response to mechanical perturbation. The common and unique genetic signatures of adaptive and maladaptive hypertrophy may be useful in the diagnosis and treatment of pathological myocardial remodeling. (Circ Cardiovasc Genet. 2009; 2: 116-124.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据