Submitted on July 19, 2006
Accepted on December 5, 2006
Altered expression of a limited number of genes contributes to cardiac decompensation during chronic ventricular tachypacing in dogs
Caroline Ojaimi1*, Khaled Qanud1, Thomas H Hintze1, and Fabio A. Recchia2
1 Physiology, New York Medical College, Valhalla, New York, United States
2 Physiology, New York Medical College, Valhalla, New York, United States; Sector of Medicine, Scuola Superiore S. Anna, Pisa, Italy
* To whom correspondence should be addressed. E-mail: caroline_ojaimi{at}nymc.edu.
Our aim was to determine the changes in the gene expression profile occurring during the transition from compensated dysfunction (CD) to decompensated heart failure (HF) in pacing-induced dilated cardiomyopathy. Twelve chronically instrumented dogs underwent left ventricular pacing at 210 beats/min for 3 weeks and at 240 beats thereafter and 4 normal dogs were used as control. The transition from CD to HF occurred between the 3rd to 4th week of pacing, with end-stage HF at 28±1 days. RNA was extracted from left ventricular tissue at control, 3 and 4 weeks of pacing (n=4) and tested with the Affymetrix Canine Array. 509 genes were differentially expressed in CD versus control (P
0.05; fold change 
±2), with 362 increasing and 147 decreasing. 526 genes were differentially expressed in HF versus control (P0.05; fold change ±2), with 439 increasing and 87 decreasing. To better understand the transition, we compared gene alterations at 3 versus 4 weeks pacing and found that only 30 genes differed (P0.05; fold change ±2). We conclude that 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 transition to overt heart failure with an unexpectedly small number of genes differentially regulated.
