Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right ventricular pressure overload.
The recent characterization of the cardiac-specific homeobox gene Nkx2-5 (or CSX) and its detection in normal adult heart tissue raises the possibility of a role in adult hypertrophy. Using pressure overload as a primary stimulus, we used a feline pulmonary artery banding model to produce right ventricular hypertrophy (RVH). Total RNA was hybridized to a full-length murine Nkx2-5 cDNA probe that contained the NK family homeodomain. Nkx2-5 mRNA levels increased 5.1-fold (P < 0.05) and 3.9-fold vs. the corresponding left ventricles at 2 and 7 days of RVH, respectively, during the period of maximal myocardial growth. By 2 wk, when the RVH response had been completed, Nkx2-5 mRNA levels were returning toward baseline. Hybridization with an Nkx2-5 probe not containing the NK homologous homeodomain demonstrated that upregulation was specific for the Nkx2-5 gene. Atrial natriuretic factor and alpha-cardiac actin, both activated in part by Nkx2-5 DNA binding elements, also increased with RVH. These data suggest that a cardiac homeobox gene may play a role in the induction of adult cardiac hypertrophy.
Thompson
J T
JT
Office of Research and Development, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA.
Rackley
M S
MS
O'Brien
T X
TX
D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002415:Cats; D006321:Heart / Q000503:physiopathology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D017380:Hypertrophy, Right Ventricular / Q000235:genetics* / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors; D015854:Up-Regulation
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors