C/EBPβ is required in pregnancy-induced cardiac hypertrophy

• Published in: International journal of cardiology Vol. 202; pp. 819 - 828
• Main Authors: Redondo-Angulo, I, Mas-Stachurska, A, Sitges, M, Giralt, M, Villarroya, F, Planavila, A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01.01.2016
• Subjects: Animals; Blotting, Western; C/EBPβ; Cardiac hypertrophy; Cardiomegaly - diagnosis; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiovascular; CCAAT-Enhancer-Binding Protein-beta - biosynthesis; CCAAT-Enhancer-Binding Protein-beta - genetics; Echocardiography; Female; Gene Expression Regulation, Developmental; Immunohistochemistry; Macrophages; Mice; Mice, Inbred C57BL; Myocardium - metabolism; Myocardium - pathology; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy, Animal; RNA - genetics; Pregnancy; C/EBPβ; Cardiac hypertrophy; Macrophages
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2015.10.005

Abstract Aim Pregnancy is a physiological model of adaptive and reversible heart enlargement, but the molecular mechanisms determining this kind of physiologic cardiac hypertrophy are poorly known. Here, we analyzed the role of the transcription factor C/EBPβ in the development of pregnancy-induced cardiac hypertrophy. Results C/EBPβ+/− mice at day 18 of gestation were used as happloinsufficiency model of late pregnancy. We found that C/EBPβ expression was specifically increased in hearts from Wt pregnant mice whereas expression of other C/EBP subtypes (α and δ) was not affected by gestation. Pregnancy-induced changes in systemic metabolic and hormonal profiles were not essentially different in Wt versus C/EBPβ+/− mice. However, C/EBPβ+/− mice developed pregnancy-induced heart hypertrophy to a lower extent relative to Wt mice. Furthermore, hearts from C/EBPβ+/− mice have alterations in fatty acid oxidation genes and reductions in the expression levels of glucose transporters that may compromise metabolic cardiac function during pregnancy. Among marker genes of inflammation, interleukin-6 (Il-6) showed a marked differential behavior in C/EBPβ+/− pregnant mice: pregnancy strongly induced cardiac Il-6 expression in wt, a phenomenon that did not occur in C/EBPβ+/− mice. Moreover, marker genes for M2 macrophages were decreased in C/EBPβ+/− pregnant mice and in C/EBPβ−/− mice subjected to LPS stimulus. Conclusions Here we found that normal levels of C/EBPβ are required for hypertrophy development during pregnancy. Events such as the increase in IL-6 in the heart of pregnant mice are prevented in C/EBPβ+/− animals. Moreover, C/EBPβ controls M2-macrophage gene expression in the heart. Thus, C/EBPβ appears as a transcription factor required for cardiac hypertrophy response to gestation.