Fetal gene program associated with right ventricular hypertrophy/failure-is left ventricle really spared?

• Published in: Journal of cardiac failure 2004-10, Vol.10 (5), p.S177-S177
• Main Authors: Shin-Ichi, Usui, Atsushi, Yao, Koichiro, Kinugawa, Toshiyuki, Takahashi, Ryozo, Nagai
• Format: Article
• Language: English
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2004.08.092

Left ventricular (LV) hypertrophy is usually associated with fetal gene program, but it remains unclear whether it is the case in right ventricular (RV) hypertrophy. Recently, an alkaloid toxin, monocrotaline (MCT), has been established to induce pulmonary hypertension and RV hypertrophy. Objective: To investigate myocyte-specific gene expression associated with RV hypertrophy/failure. Methods: Rats were injected with MCT (50mg/kg) and after 6 weeks levels of mRNA expression were determined. ∗P < 0.05 vs vehicle. Results: Approximately half of MCT-injected rats died after 6 weeks. MCT markedly increased RV weight (289% ∗) with modest increases in LV weight (148% ∗). In MCT-treated RV, the mRNA level of SERCA (34.6% ∗) or alpha-MHC (12.8%∗) was decreased, while that of ANP (1100% ∗), BNP (1100% ∗), skeletal alpha-actin (462% ∗), or beta-MHC (313% ∗) was increased, i.e. fetal gene program activation. Interestingly, not only in septum but in separated LV free wall, MCT also activated significant fetal gene program except SERCA. Conclusion: MCT induced RV hypertrophy and failure, which was accompanied by typical fetal gene program in RV. Although MCT theoretically caused unloading of LV free wall, MCT-treated LV exhibited similar pattern of fetal gene activation. Thus, LV may also be affected in the case of severe pulmonary hypertension. The induction of fetal gene program in LV might be attributable to paracrine effects of neurohormonal factors produced by diseased pulmonary vasculature and/or RV.