A change of heart: Understanding the mechanisms regulating cardiac proliferation and metabolism before and after birth.

Mammalian cardiomyocytes undergo major maturational changes in preparation for birth and postnatal life. Immature cardiomyocytes contribute to cardiac growth via proliferation and thus the heart has the capacity to regenerate. To prepare for postnatal life, structural and metabolic changes associated with increased cardiac output and function must occur. This includes exit from the cell cycle, hypertrophic growth, mitochondrial maturation and sarcomeric protein isoform switching. However, these changes come at a price; the loss of cardiac regenerative capacity such that damage to the heart in postnatal life is permanent. This is a significant barrier in the development of new treatments for cardiac repair and contributes to heart failure. The transitional period of cardiomyocyte growth is a complex and multifaceted event. In this review, we focus on studies that have investigated this critical transition period as well as novel factors that may regulate and drive this process. We also discuss the potential use of new biomarkers for the detection of myocardial infarction and in the broader sense, cardiovascular disease. Abstract figure legend In the mammalian fetal (immature) heart, cardiomyocytes proliferate and can regenerate in a low oxygen environment. In the lead up to and after birth, major changes occur to cardiomyocytes that result in regeneration no longer being possible; however, timing of these events varies across species. Factors that regulate this cardiomyocyte transition include nutrient and oxygen availability, hormones and microRNAs. An emerging field of research is the use of biomarkers as a non-invasive detection method for cardiovascular disease. This article is protected by copyright. All rights reserved.