Abstract 134: Differential Regulation of Extracellular Matrix Remodeling Enzymes in Physiological vs Pathological Heart Hypertrophy
Introduction. Remodeling of the cardiac Extracellular Matrix(ECM) is important in both pathological and physiological cardiac hypertrophy. However, the differences in ECM gene expression between these two hypertrophies are not well characterized. We hypothesize that metalloproteinases ADAM15 and ADAM17 and matricellular fetal gene osteopontin (OPN) are differentially expressed during pathologic and physiologic heart hypertrophy.
Methods. Pathological RV hypertrophy was induced in rats by monocrotaline(MCT, 60mg/kg, s.c.). Estrogen therapy (42.5ug/kg/day) was started in some rats 21 days post MCT for 10 days. Late pregnant mice with physiologic cardiac hypertrophy were compared to non-pregnant mice. Relative gene expression was measured by RT-PCR. P<0.05 was considered significant. Values are given mean±SE.
Results. Late pregnant mice developed cardiac hypertrophy compared to non pregnant controls(heart weight =0.124±0.002g. vs 0.104±0.002g, p<0.01). MCT treated rats developed RV hypertrophy compared to saline treated controls (RV/LV+IVS=0.69±0.07 vs 0.26±0.02 in CTRL, p<0.05). ADAM15 and ADAM17 were significantly elevated in the RV of MCT treated rats (2.5 fold and 1.5 fold resp. vs CTRL, p<0.05). By contrast, both ADAMs were decreased 50% in the myocardium of late pregnant vs non pregnant (all p<0.05). OPN was upregulated 10-fold in RV hypertrophy rats (p<0.01) whereas it was not detected in late pregnant mice. Estrogen treatment of RV hypertrophy animals reverses elevated expression of ADAM15, ADAM17 and OPN to control levels (all p<.05). Elevated levels of estrogen present in late pregnancy could account for the regulation of these remodeling enzymes during physiologic hypertrophy.
Conclusion: Physiological cardiac hypertrophy differs from pathological hypertrophy in the expression of extracellular matrix remodeling enzymes ADAM15, ADAM17 and OPN. Estrogen may play an important role in the regulation of these enzymes during physiologic hypertrophy.
- © 2011 by American Heart Association, Inc.