scholarly journals Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart

2013 ◽  
Vol 5 (2) ◽  
pp. 191-209 ◽  
Author(s):  
Konstantinos Malliaras ◽  
Yiqiang Zhang ◽  
Jeffrey Seinfeld ◽  
Giselle Galang ◽  
Eleni Tseliou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cell ◽  
Adult Mouse ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Cell Recruitment

scholarly journals Conditional Transgenic Expression of Fibroblast Growth Factor 9 in the Adult Mouse Heart Reduces Heart Failure Mortality After Myocardial Infarction

Circulation ◽  
2011 ◽  
Vol 123 (5) ◽  
pp. 504-514 ◽  
Author(s):  
Mortimer Korf-Klingebiel ◽  
Tibor Kempf ◽  
Klaus-Dieter Schlüter ◽  
Christian Willenbockel ◽  
Torben Brod ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Adult Mouse ◽  
Mouse Heart ◽  
Fibroblast Growth ◽  
Transgenic Expression

Abstract 10: Cardiac-specific Yap Activation Improve Cardiac Function And Survival In An Experimental Murine Mi Model

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Zhiqiang Lin ◽  
Alexander von Gise ◽  
Pingzhu Zhou ◽  
Qing Ma ◽  
Jinghai Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Cardiac Function ◽  
Heart Function ◽  
Expression System ◽  
Gene Expression Signature ◽  
Cell Cycle Gene ◽  
Mouse Heart ◽  
Hippo Signaling ◽  
Cardiomyocyte Proliferation

Background: Yes-Associated Protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte proliferation. We hypothesized that YAP activation after myocardial infarction would preserve cardiac function and improve survival. Methods and Results: In this study, we used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated cell cycle gene expression, activated of components of the inflammatory response, and promoted a less mature cardiac gene expression signature. Conclusions: Cardiac specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI.

scholarly journals Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction

2019 ◽  
Vol 40 (30) ◽  
pp. 2507-2520 ◽  
Author(s):  
Ziwen Li ◽  
Emmanouil G Solomonidis ◽  
Marco Meloni ◽  
Richard S Taylor ◽  
Rodger Duffin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Single Cell ◽  
Adult Mouse ◽  
Bone Marrow Cells ◽  
Lineage Tracing ◽  
Border Region ◽  
Mouse Heart ◽  
Ischaemic Injury ◽  
Mesenchymal Transition

AbstractAimsA better understanding of the pathways that regulate regeneration of the coronary vasculature is of fundamental importance for the advancement of strategies to treat patients with heart disease. Here, we aimed to investigate the origin and clonal dynamics of endothelial cells (ECs) associated with neovascularization in the adult mouse heart following myocardial infarction (MI). Furthermore, we sought to define murine cardiac endothelial heterogeneity and to characterize the transcriptional profiles of pro-angiogenic resident ECs in the adult mouse heart, at single-cell resolution.Methods and resultsAn EC-specific multispectral lineage-tracing mouse (Pdgfb-iCreERT2-R26R-Brainbow2.1) was used to demonstrate that structural integrity of adult cardiac endothelium following MI was maintained through clonal proliferation by resident ECs in the infarct border region, without significant contributions from bone marrow cells or endothelial-to-mesenchymal transition. Ten transcriptionally discrete heterogeneous EC states, as well as the pathways through which each endothelial state is likely to enhance neovasculogenesis and tissue regeneration following ischaemic injury were defined. Plasmalemma vesicle-associated protein (Plvap) was selected for further study, which showed an endothelial-specific and increased expression in both the ischaemic mouse and human heart, and played a direct role in regulating human endothelial proliferation in vitro.ConclusionWe present a single-cell gene expression atlas of cardiac specific resident ECs, and the transcriptional hierarchy underpinning endogenous vascular repair following MI. These data provide a rich resource that could assist in the development of new therapeutic interventions to augment endogenous myocardial perfusion and enhance regeneration in the injured heart.

scholarly journals Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Christian Bär ◽  
Bruno Bernardes de Jesus ◽  
Rosa Serrano ◽  
Agueda Tejera ◽  
Eduard Ayuso ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Adult Mouse ◽  
Mouse Heart

scholarly journals Mammalian Cardiac Regeneration After Fetal Myocardial Infarction Requires Cardiac Progenitor Cell Recruitment

2013 ◽  
Vol 96 (1) ◽  
pp. 163-170 ◽  
Author(s):  
Myron Allukian ◽  
Junwang Xu ◽  
Michael Morris ◽  
Robert Caskey ◽  
Wanda Dorsett-Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cell ◽  
Cardiac Regeneration ◽  
Cell Recruitment ◽  
Cardiac Progenitor Cell
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