Postprandial cardiac hypertrophy is sustained by mechanics, epigenetic, and metabolic reprogramming in pythons

• 成果类型: Article
• 署名作者: Crocini, Claudia; Woulfe, Kathleen C.; Ozeroff, Christopher D.; Perni, Stefano; Cardiello, Joseph; Walker, Cierra J.; Wilson, Cortney E.; Anseth, Kristi; Allen, Mary Ann; Leinwand, Leslie A.
• 署名单位: Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Colorado System; University of Colorado Anschutz Medical Campus
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12790
• DOI: 10.1073/pnas.2322726121
• 发表日期: 2024-09-03
• 关键词: yin yang 1; burmese python; heart-rate; transcriptome analysis; blood-flow; muscle; digestion; yy1; responses; protein

摘要

Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was to investigate how python hearts achieve this adaptive response after feeding. Isolated myofibrils increased force after feeding without changes in sarcomere ultrastructure and without increasing energy cost. Ca2+ transients were prolonged after feeding with in decreased cardiac tissue stiffness. Feeding also reduced the activity of sirtuins, a metabolically linked class of histone deacetylases, and increased chromatin accessibility. Transcription factor enrichment analysis on transposase- accessible chromatin with sequencing revealed the prominent role of transcription factors Yin Yang1 and NRF1 in postfeeding cardiac adaptation. Gene expression also changed with the enrichment of translation and metabolism. Finally, metabolomics analysis and adenosine triphosphate production demonstrated that cardiac adaptation after feeding not only increased energy demand but also energy production. These findings have broad implications for our understanding of cardiac adaptation across species and hold promise for the development of innovative approaches to address cardiovascular diseases.