Transition from compensated hypertrophy to systolic heart failure in the spontaneously hypertensive rat: Structure, function, and transcript analysis

Wesley W. Brooks, Steven S. Shen, Chester H. Conrad, Ronald H. Goldstein, Oscar H L Bing

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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-β 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.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalGenomics
Volume95
Issue number2
DOIs
StatePublished - Feb 2010

Bibliographical note

Funding Information:
This work was supported by Medical Research Funds provided to WWB from the Department of Veterans Affairs. We are particularly grateful to Dr. Marc Lenburg of the Genomics Department at Boston University School of Medicine for his help in carrying out the data acquisition and statistical analysis of the Affymetrix GeneChip data.

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • Cardiac hypertrophy
  • Gene expression microarray
  • Heart failure
  • Hypertension

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