VA Boston Healthcare System, Boston, MA 02130, USA.
Genomics. 2010 Feb;95(2):84-92. doi: 10.1016/j.ygeno.2009.12.002. Epub 2009 Dec 16.
Gene expression, determined by micro-array analysis, and left ventricular (LV) remodeling associated with the transition to systolic heart failure (HF) were examined in the spontaneously hypertensive rat (SHR). By combining transcript and gene set enrichment analysis (GSEA) of the LV with assessment of function and structure in age-matched SHR with and without HF, we aimed to better understand the molecular events underlying the onset of hypertensive HF. Failing hearts demonstrated depressed LV ejection fraction, systolic blood pressure, and LV papillary muscle force while LV end-diastolic and systolic volume and ventricular mass increased. 1431 transcripts were differentially expressed between failing and non-failing animals. GSEA identified multiple enriched gene sets, including those involving inflammation, oxidative stress, cell degradation and cell death, as well as TGF-beta and insulin signaling pathways. Our findings support the concept that these pathways and mechanisms may contribute to deterioration of cardiac function and remodeling associated with hypertensive HF.
通过微阵列分析来确定基因表达，并对与向收缩性心力衰竭（HF）转变相关的左心室（LV）重构进行研究，研究对象为自发性高血压大鼠（SHR）。通过将 LV 的转录组和基因集富集分析（GSEA）与对年龄匹配的 SHR 中有无 HF 的功能和结构进行评估相结合，我们旨在更好地了解高血压 HF 发生的分子事件。衰竭心脏表现出 LV 射血分数、收缩压和 LV 乳头肌力量降低，而 LV 舒张末期和收缩末期容积以及心室质量增加。在衰竭和非衰竭动物之间有 1431 个转录本存在差异表达。GSEA 确定了多个富集的基因集，包括涉及炎症、氧化应激、细胞降解和细胞死亡的基因集，以及 TGF-β和胰岛素信号通路。我们的研究结果支持以下观点，即这些途径和机制可能与高血压 HF 相关的心脏功能恶化和重构有关。
