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Altered Expression of a Limited Number of Genes Contributes to Cardiac Decompensation During Chronic Pacing in the Conscious Dog
Author(s) -
Ojaimi Caroline,
Hintze Thomas H,
Recchia Fabio A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1187-c
Subject(s) - decompensation , cardiac decompensation , cardiology , gene , medicine , biology , heart failure , genetics
We have used chronic cardiac pacing in conscious dogs to study mechanism related to the development of dilated cardiomyopathy and the transition from compensated dysfunction (CD) to decompensated heart failure (HF). This occurs from the 3rd to 4th week of pacing with end‐stage HF at 30±1 days. Indices of cardiac contractility are reduced progressively from control to 21 days and further fall between 21 and 28 days. This is associated with a rise in LV end‐diastolic pressure to 15±3 mmHg at 21 days and 25±2 mmHg at 28 days. In this study we used the Affymetrix Canine Array to determine differential expression of potential target genes during the progression to decompensation. Cardiac RNA was extracted at control, 3 and 4 weeks of pacing (n=4). From control to CD, 184 genes were differentially expressed (P<0.05; fold change of at least ±1.5), 124 increasing and 60 decreasing. From control to HF the expression of 208 genes changed, 142 increasing and 66 decreasing. To better understand the transition, we divided the HF group by the CD group and the analysis showed that 56 genes differed. Because 208 minus 184 is only 24, while we measured 56 genes that had changed, this means that some genes over‐expressed at 3 weeks had to decline so that they were no longer statistically significant. In addition, this means that only 32 genes were up‐or down‐regulated between CD and HF. A number of processes including normalization of gene regulation during decompensation, appearance of new up‐regulated genes and maintenance of gene expression all contribute to the development of cardiac decompensation with an unexpectedly small number of genes differentially regulated. Supported by HL‐PO1‐43023 grant.