Cardiovascular diseases are the leading cause of death globally, with no cure currently. Therefore, there is a dire need to further understand the mechanisms that arise during heart failure. Notoriously, the adult mammalian heart has a very limited ability to regenerate its functional cardiac cells, cardiomyocytes, after injury. However, the neonatal mammalian heart has a window of regeneration that allows for the repair and renewal of cardiomyocytes after injury. This specific timeline has been of interest in the field of cardiovascular and regenerative biology as a potential target for adult cardiomyocyte repair. Recently, many of the neonatal cardiomyocyte regeneration mechanisms have been associated with epigenetic regulation within the heart. This review summarizes the current and most promising epigenetic mechanisms in neonatal cardiomyocyte regeneration, with a specific emphasis on the potential for targeting these mechanisms in adult cardiac models for repair after injury.

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

With the global impact of cardiovascular disease, there is a dire need to understand the mechanisms in the heart during injury and stress. It has been shown that the regulation of the extracellular matrix via cardiac fibroblasts plays a major role in the progression of heart failure and worsening function of the heart. Importantly, it has been suggested that crosstalk between other cardiac cells like cardiomyocytes, immune cells, and endothelial cells are influenced by the pathological function of the fibroblasts. This decline in function across all cardiac cells is seemingly irreversible. However, epigenetic mechanisms have been shown to regulate functionality across cardiac cells and improve outcomes during stress or injury. This epigenetic regulation has also been shown to control communication between different cell types and influence the role of multiple cardiac cell types during injury. The goal of this review is to summarize and discuss the current research of epigenetic regulation of cardiac fibroblasts and the subsequent crosstalk with other cardiac cell types in cardiovascular disease states.

Cardiovascular diseases are a major cause of death globally, with no cure to date. Many interventions have been studied and suggested, of which epigenetics and chromatin remodeling have been the most promising. Over the last decade, major advancements have been made in the field of chromatin remodeling, particularly for the treatment of heart failure, because of innovations in bioinformatics and gene therapy. Specifically, understanding changes to the chromatin architecture have been shown to alter cardiac disease progression via variations in genomic sequencing, targeting cardiac genes, using RNA molecules, and utilizing chromatin remodeler complexes. By understanding these chromatin remodeling mechanisms in an injured heart, treatments for heart failure have been suggested through individualized pharmaceutical interventions as well as biomarkers for major disease states. By understanding the current roles of chromatin remodeling in heart failure, a potential therapeutic approach may be discovered in the future.

The effect of air pollution on health is listed as a significant cause of death worldwide. Slightly over 3 million deaths per year are due to outdoor air pollution. Studies have shown that short term increases in exposure to particulate matter have increased the risk of cardiovascular diseases such as myocardial infarction, stroke, and heart failure. However, less is known about the longer term effects of air pollution on various cardiovascular diseases. The American Heart Association formally recognized PM2.5 as a significant cardiovascular risk factor in 2010. Since then, more prolonged term exposure to air pollution has been suggested to cause chronic cardiometabolic and cardiovascular problems. The effects of long term (>3 years) air pollution are significant, but not as much is known about how location affects this exposure. Associations with cardiovascular diseases and their risk factors are often increased in urban settings, which is attributed to a higher concentrations of outdoor air pollution, independent of ethnic groups and seasonal changes. Potential causes of long term air pollution concentrations in cities or metropolitan areas come from traffic exposure and traffic intensity. The Environmental Protection Agency and United Nations have suggested changes in air quality standards, implementation plans, and ways to reduce vehicle emissions specifically to improve human health and reduce the adverse effects of air pollution; however, more work still needs to be done. This review assesses the impact of the global long term (>3 years) air pollution exposure, specifically in urban environments on cardiovascular health and disease.