| The calcineurin-NFAT (nuclear factor of activated T-cell) signaling cascade appears to play a critical role in the progression of cardiovascular diseases such as dilated cardiomyopathy and heart failure (HF). The underlying mechanism by which this cascade influences outcomes on physiological vs. pathological hypertrophy remains elusive, in particular whether its principal role is to initiate or only to maintain hypertrophy. A meta-analysis was performed using microarray results from two experiment models of left ventricular cardiac hypertrophy: pressure-overload induced pathological hypertrophy by aortic banding and exercise-induced physiological hypertrophy by swimming. The lack of common controls between the two experiments required unique data handling routines, including a restriction to measurements falling in the linear detection range for each experiment that enable meaningful comparison of the data sets. Microarrays measure the levels of portions of transcripts represented by the probe sequences: of genes known to be important in the targeted processes, MCIP1 (modulatory calcineurin-interacting protein-1) transcript increased but that of Kv4.3, which encodes the repolarizing transient outward K + current Ito, decreased in response to hemodynamic stress. Neither gene changed significantly in exercise-induced cardiac hypertrophy, suggesting that this signaling cascade is not significantly affected in this condition and hence, a different mechanism for hypertrophy leads to the same phenotypic outcome in the two models of hypertrophy. The results of a comparison of many modulated genes suggest a possible signaling mechanism for the pressure-overload induced hypertrophy condition. |
