Pathological and physiological hypertrophies are regulated by distinct gene programs

Abstract

Background: : This study aims to investigate changes that occur during progression and establishment of physiological and pathological cardiac hypertrophy, by microarray technology and functional annotations. DESIGN AND METHODS: Myocardial infarction leading to heart failure was induced in rats, with animals killed 1, 3, 7, 14, 42, and 92 days after coronary artery ligation. A second group was subjected to daily treadmill exercise and killed 1, 4, 24, and 48 h after a single exercise bout, or after 28 or 56 days of exercise training. Results: Physiological hypertrophy was associated with less transcriptional alternation than pathological hypertrophy, indicating that posttranscriptional and translational regulation may be more important. The main difference between the two types of hypertrophy was that myocardial infarction was associated with downregulation of genes related to fatty acid metabolism, whereas no such change occurred after exercise training. Thus, fatty acid metabolism may distinguish adverse maladaptive hypertrophy from beneficial adaptive hypertrophy. Conclusion: This study points to specific genes and gene classes related to biological processes that may be important in these well-characterized rat models of physiological and pathological cardiac hypertrophy. © 2009 The European Society of Cardiology.