Transcriptome analysis of cardiac endothelial cells after myocardial infarction reveals temporal changes and long-term deficits

• Published in: Scientific reports Vol. 14; no. 1; p. 9991
• Main Authors: Basu, Chitra, Cannon, Presley L., Awgulewitsch, Cassandra P., Galindo, Cristi L., Gamazon, Eric R., Hatzopoulos, Antonis K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 692/4019; 692/4019/592; 692/4019/592/75/2/1674; Animals; Cell activation; Cell cycle; Cell Movement - genetics; Cell Proliferation; Circadian rhythms; Congestive heart failure; Disease Models, Animal; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; G2 phase; Gene Expression Profiling; Heart attacks; Heart diseases; Humanities and Social Sciences; Inflammation; Ischemia; Long-term effects; Male; Metabolic pathways; Metabolic rate; Metabolism; Mice; Mice, Inbred C57BL; Mitosis; multidisciplinary; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardium - metabolism; Myocardium - pathology; Phenotypes; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Rac1 protein; S phase; Science; Science (multidisciplinary); Transcriptome; Transcriptomes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-59155-8

Endothelial cells (ECs) have essential roles in cardiac tissue repair after myocardial infarction (MI). To establish stage-specific and long-term effects of the ischemic injury on cardiac ECs, we analyzed their transcriptome at landmark time points after MI in mice. We found that early EC response at Day 2 post-MI centered on metabolic changes, acquisition of proinflammatory phenotypes, initiation of the S phase of cell cycle, and activation of stress-response pathways, followed by progression to mitosis (M/G2 phase) and acquisition of proangiogenic and mesenchymal properties during scar formation at Day 7. In contrast, genes involved in vascular physiology and maintenance of vascular tone were suppressed. Importantly, ECs did not return to pre-injury phenotypes after repair has been completed but maintained inflammatory, fibrotic and thrombotic characteristics and lost circadian rhythmicity. We discovered that the highest induced transcript is the mammalian-specific Sh2d5 gene that promoted migration and invasion of ECs through Rac1 GTPase. Our results revealed a synchronized, temporal activation of disease phenotypes, metabolic pathways, and proliferation in quiescent ECs after MI, indicating that precisely-timed interventions are necessary to optimize cardiac tissue repair and improve outcomes. Furthermore, long-term effects of acute ischemic injury on ECs may contribute to vascular dysfunction and development of heart failure.