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.