Related Experiment Video
Updated: Dec 12, 2025
Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
Published on: August 28, 2016
p300 in Cardiac Development and Accelerated Cardiac Aging
1Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Insights
Epigenetic regulator Acetyltransferase p300 (p300) is crucial for heart development and function. Targeting p300 activity may prevent cardiac aging and heart failure, offering a new therapeutic strategy for heart disease.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Developmental Biology
Background:
- Heart disease is the leading global cause of death, linked to congenital defects and acquired adult dysfunctions.
- Epigenetics, particularly the role of Acetyltransferase p300 (p300), is critical in embryonic heart development and adult heart disease.
- Stress-induced pathways accelerate cardiac aging, leading to pathologies like hypertrophy, cardiomyopathy, and heart failure.
Purpose of the Study:
- To elucidate the role of Acetyltransferase p300 (p300) in embryonic heart development and adult cardiac pathologies.
- To investigate the epigenetic mechanisms by which p300 regulates cardiac gene expression.
- To explore the therapeutic potential of targeting p300 for preventing or treating accelerated cardiac aging and heart failure.
Main Methods:
- Examined the impact of p300 deficiency/abnormal expression on embryonic heart and neural tube development.
- Analyzed p300's role in epigenetic control of cardiac gene expression in adult hearts.
- Investigated p300 deregulation in response to hypertrophic and fibrogenic stress signals.
- Reviewed preclinical studies on pharmacologic or genetic normalization of p300 activity.
Main Results:
- p300 is essential for embryonic heart development; its deficiency causes embryonic lethality due to cardiac and neural tube deformities.
- p300 controls cardiac development via histone acetylation-mediated chromatin remodeling and transcriptional regulation.
- In adult hearts, p300 is differentially expressed and epigenetically regulates cardiac genes.
- Deregulation of p300 is linked to cardiac hypertrophy and fibrosis, common in aging-related heart conditions.
- Preclinical studies show normalizing p300 activity can prevent or halt cardiac aging pathologies.
Conclusions:
- Acetyltransferase p300 (p300) is a pivotal epigenetic regulator in both embryonic heart development and adult cardiac health.
- Dysregulation of p300 contributes to stress-induced cardiac aging, hypertrophy, and fibrosis.
- Targeting p300 with small molecule inhibitors presents a promising therapeutic strategy to combat accelerated cardiac aging and reduce heart disease mortality.
Abstract:
The heart is the first functional organ that develops during embryonic development. While a heartbeat indicates life, cessation of a heartbeat signals the end of life. Heart disease, due either to congenital defects or to acquired dysfunctions in adulthood, remains the leading cause of death worldwide. Epigenetics plays a key role in both embryonic heart development and heart disease in adults. Stress-induced vascular injury activates pathways involved in pathogenesis of accelerated cardiac aging that includes cellular dysfunction, pathological cardiac hypertrophy, diabetic cardiomyopathy, cardiac matrix remodeling, cardiac dysfunction and heart failure. Acetyltransferase p300 (p300), a major epigenetic regulator, plays a pivotal role in heart development during embryogenesis, as deficiency or abnormal expression of p300 leads to embryonic death at early gestation periods due to deformation of the heart and neural tube. Acetyltransferase p300 controls heart development through histone acetylation-mediated chromatin remodeling and transcriptional regulation of genes required for cardiac development. In adult hearts, p300 is differentially expressed in different chambers and epigenetically controls cardiac gene expression. Deregulation of p300, in response to prohypertrophic and profibrogenic stress signals, is associated with increased recruitment of p300 to several genes including transcription factors, increased acetylation of specific lysines in histones and transcription factors, altered chromatin organization, and increased hypertrophic and fibrogenic gene expression. Cardiac hypertrophy and myocardial fibrogenesis are common pathological manifestations of several stress-induced accelerated cardiac aging-related pathologies, including high blood pressure-induced or environmentally induced cardiac hypertrophy, myocardial infarction, diabetes-induced cardiomyopathy, and heart failure. Numerous studies using cellular and animal models clearly indicate that pharmacologic or genetic normalization of p300 activity has the potential to prevent or halt the progression of cardiac aging pathologies. Based on these preclinical studies, development of safe, non-toxic, small molecule inhibitors/epidrugs targeting p300 is an ideal approach to control accelerated cardiac aging-related deaths worldwide.
