Distinct Cardiac Transcriptional Profiles Defining Pregnancy and Exercise

Abstract

BackgroundAlthough the hypertrophic responses of the heart to pregnancy and exercise are both considered to be physiological processes, they occur in quite different hormonal and temporal settings. In this study, we have compared the global transcriptional profiles of left ventricular tissues at various time points during the progression of hypertrophy in exercise and pregnancy.Methodology/Principal FindingsThe following groups of female mice were analyzed: non-pregnant diestrus cycle sedentary control, mid-pregnant, late-pregnant, and immediate-postpartum, and animals subjected to 7 and 21 days of voluntary wheel running. Hierarchical clustering analysis shows that while mid-pregnancy and both exercise groups share the closest relationship and similar gene ontology categories, late pregnancy and immediate post-partum are quite different with high representation of secreted/extracellular matrix-related genes. Moreover, pathway-oriented ontological analysis shows that metabolism regulated by cytochrome P450 and chemokine pathways are the most significant signaling pathways regulated in late pregnancy and immediate-postpartum, respectively. Finally, increases in expression of components of the proteasome observed in both mid-pregnancy and immediate-postpartum also result in enhanced proteasome activity. Interestingly, the gene expression profiles did not correlate with the degree of cardiac hypertrophy observed in the animal groups, suggesting that distinct pathways are employed to achieve similar amounts of cardiac hypertrophy.Conclusions/SignificanceOur results demonstrate that cardiac adaptation to the later stages of pregnancy is quite distinct from both mid-pregnancy and exercise. Furthermore, it is very dynamic since, by 12 hours post-partum, the heart has already initiated regression of cardiac growth, and 50 genes have changed expression significantly in the immediate-postpartum compared to late-pregnancy. Thus, pregnancy-induced cardiac hypertrophy is a more complex process than exercise-induced cardiac hypertrophy and our data suggest that the mechanisms underlying the two types of hypertrophy have limited overlap.

S-Enantiomer of 19-Hydroxyeicosatetraenoic Acid Preferentially Protects Against Angiotensin II-Induced Cardiac Hypertrophy

“…The first metabolic pathway is P450 enzymes, particularly CYP1B1. CYP1B1 is constitutively expressed in the cardiac tissue, and several reports have confirmed the association between this enzyme and cardiovascular disease states (Zordoky and El-Kadi, 2008;Chung et al, 2012). For example, blood pressure elevation induced by Ang II was reduced in Cyp1b1-null mice compared with wildtype mice (Jennings et al, 2010).…”

Metabolic Coordination of Physiological and Pathological Cardiac Remodeling

“… 159 , 160 Nevertheless, the mild cardiac dysfunction during pregnancy is usually not of concern because it reverses in the postpartum period. 161 This fact, combined with the increase in angiogenesis, 162 , 163 lack of fibrosis, 151 , 162 , 164 , 165 and protection against some forms of stress 166 – 168 in the pregnancy-adapted heart, help to assign pregnancy-induced cardiac growth as a physiological form of hypertrophy.…”

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

“…Numerous studies have documented cardiac transcriptomic changes following exercise training (Budiono et al, 2012; Chung et al, 2012; Iemitsu et al, 2005; Solskov et al, 2012; Strom et al, 2005). The results of these studies indicate that re-progamming of cardiac structure and function during cardiac growth, whether due to exercise or pathologic stimuli, involves a cascade of gene regulatory mechanisms.…”