scholarly journals Reactivation of atrium genes is a primer for heart infarction or regeneration

2020 ◽  
Author(s):  
Yisong Zhen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Bioinformatics Analysis ◽  
Morbidity And Mortality ◽  
Cardiomyocyte Proliferation ◽  
Cell Type ◽  
Adult Heart ◽  
Heart Infarction ◽  
Analysis Methods

AbstractThe inability of the adult heart to repair or regenerate is manifested in prevalent morbidity and mortality related to myocardial infarction and heart failure. However, the cue to the reactivation of cardiomyocyte proliferation in the adult remains largely unknown. In the present study, three independent datasets were explored using bioinformatics analysis methods to solve the problem. Our results revealed that atrium genes were upregulated in response to the injury, which indicates the possible cell type withdraw and reinitiation of proliferation capability. Our findings might provide an alternative viewpoint on the cardiomyocyte regeneration or myocardial infarction.

Abstract 55: Opposing Roles Of Distinct Macrophage Lineages In Heart Failure And Cardiac Recovery

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Kory J Lavine ◽  
Slava Epelman ◽  
Keita Uchida ◽  
Kassandra J Weber ◽  
Joel D Schilling ◽  
...  
Keyword(s):  
Heart Failure ◽  
Tissue Repair ◽  
Cardiomyocyte Proliferation ◽  
New Paradigm ◽  
Chemokine Production ◽  
Adult Heart ◽  
Cardiac Recovery ◽  
Novel Treatments ◽  
Inflammatory Monocytes ◽  
Embryonic Origin

Why inflammation is simultaneously deleterious following injury and essential for tissue repair continues to be fundamentally important and debated question. Recently, a new paradigm has emerged in the macrophage field: that organs are replete with resident macrophages of embryonic origin, distinct from monocyte-derived macrophages. This added complexity raises the question of whether distinct immune cells drive inflammatory and reparative activities following injury. Previous work has demonstrated that the neonatal heart has a remarkable capacity for tissue repair compared to the adult, offering an ideal context to examine these concepts. We hypothesized that unrecognized differences in macrophage composition in the neonatal and adult heart represents a key determinant of cardiac recovery. To test this hypothesis, we generated a novel cardiomyocyte ablation model and demonstrated that following injury neonatal mice expand a population of resident cardiac macrophages derived from embryonic lineages, which generate minimal inflammation and are necessary and sufficient for cardiac recovery through promotion of cardiomyocyte proliferation and angiogenesis. During homeostasis the adult heart also contained embryonic-derived macrophages with similar properties. However, following injury these cells disappeared, and instead, the adult heart recruited pro-inflammatory monocytes and monocyte-derived macrophages that lacked reparative activities. Inhibition of monocyte recruitment into the injured adult heart preserved embryonic-derived macrophage subsets, reduced inflammatory cytokine and chemokine production, and enhanced tissue repair. Together, these findings indicate that embryonic-derived macrophages, rather than monocyte-derived macrophages, are key mediators of cardiac recovery. Therapeutics targeting distinct macrophage and monocyte lineages may serve as novel treatments for heart failure.

scholarly journals Evidence for minimal cardiogenic potential of Sca-1 positive cells in the adult mouse heart

2018 ◽  
Author(s):  
Lauren E. Neidig ◽  
Florian Weinberger ◽  
Nathan J. Palpant ◽  
John Mignone ◽  
Amy M. Martinson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Mouse Model ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Genetic Lineage ◽  
Adult Heart ◽  
New Therapeutic Approaches ◽  
Genetic Lineage Tracing

ABSTRACTBackgroundDespite modern pharmacotherapy, heart failure remains a major medical burden. The heart has a limited regenerative capacity, and bolstering regeneration might represent new therapeutic approaches for heart failure patients. Various progenitor cells in the heart have been proposed to have cardiomyogenic properties, but this evidence is based mostly on cell culture and transplantation studies. One population of interest is characterized by the expression of Stem Cell Antigen-1 (Sca-1). Here we tested the hypothesis that Sca-1+cells are endogenous progenitors for cardiomyocytes in the adult heart.MethodsWe evaluated the innate cardiogenic potential of Sca-1+cellsin vivoby generating a novel mouse model to genetically lineage-trace the fate of Sca-1 expressing cells. This was accomplished by introducing a tamoxifen-inducible Cre-recombinase into the Sca-1 locus (Sca-1mCm/+). Crossing this mouse line to a Cre-dependent tdTomato reporter line allowed for genetic lineage-tracing of endogenous Sca-1+cells (Sca-1mCmR26tdTomato). The frequency of Sca-1+cardiomyocytes was quantified from dispersed cell preparations and confirmed by in situ histology.ResultsWe validated the genetic lineage tracing mouse model in bone marrow and heart. Unlike previous publications suggesting significant cardiogenic potential, we found that less than 0.02% of cardiomyocytes per year were derived from Sca-1+cells in the adult heart under homeostatic conditions. At six months after myocardial infarction, we found less than 0.01% of cardiomyocytes were derived from Sca-1+cells.ConclusionOur results show that Sca-1+cells in the adult heart have minimal cardiogenic potential under homeostatic conditions or in response to myocardial infarction.

scholarly journals The role of neuregulin/ErbB2/ErbB4 signaling in the heart with special focus on effects on cardiomyocyte proliferation

2012 ◽  
Vol 302 (11) ◽  
pp. H2139-H2147 ◽  
Author(s):  
Brian Wadugu ◽  
Bernhard Kühn
Keyword(s):  
Heart Failure ◽  
Cardiac Development ◽  
Current Knowledge ◽  
Critical Role ◽  
Special Focus ◽  
Cardiomyocyte Proliferation ◽  
Neuregulin 1 ◽  
Adult Heart ◽  
Signaling Complex ◽  
And Function

The signaling complex consisting of the growth factor neuregulin-1 (NRG1) and its tyrosine kinase receptors ErbB2 and ErbB4 has a critical role in cardiac development and homeostasis of the structure and function of the adult heart. Recent research results suggest that targeting this signaling complex may provide a viable strategy for treating heart failure. Clinical trials are currently evaluating the effectiveness and safety of intravenous administration of recombinant NRG1 formulations in heart failure patients. Endogenous as well as administered NRG1 has multiple possible activities in the adult heart, but how these are related is unknown. It has recently been demonstrated that NRG1 administration can stimulate proliferation of cardiomyocytes, which may contribute to repair failing hearts. This review summarizes the current knowledge of how NRG1 and its receptors control cardiac physiology and biology, with special emphasis on its role in cardiomyocyte proliferation during myocardial growth and regeneration.

Cardiomyocyte proliferation and protection against post-myocardial infarction heart failure by cyclin D1 and Skp2 ubiquitin ligase

2008 ◽  
Vol 80 (2) ◽  
pp. 181-190 ◽  
Author(s):  
Mimi Tamamori-Adachi ◽  
Hiromitsu Takagi ◽  
Kimio Hashimoto ◽  
Kazumichi Goto ◽  
Toshinori Hidaka ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cyclin D1 ◽  
Ubiquitin Ligase ◽  
Post Myocardial Infarction ◽  
Cardiomyocyte Proliferation ◽  
Infarction Heart

Identification of Key Genes and Signaling Pathways Involved in Acute Myocardial Infarction and Potential Biomarkers of Its Consequent Heart Failure Based On Bioinformatics Analysis

2021 ◽  
Author(s):  
Yuyan Xiong ◽  
Yuejin Yang
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Bioinformatics Analysis ◽  
Roc Curves ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Key Genes ◽  
Potential Biomarkers

Abstract Backgrounds : Acute myocardial infarction (AMI) is the predominant cause of cardiac death and ischemic heart failure (IHF) worldwide in coronary artery disease (CAD). Although it results from coronary acute occlusion, we in the study explored some key genes involved in the development of AMI and consequent IHF using bioinformatics analysis. Methods Utilizing expression data of 52 patients with AMI and 53 controls from GSE66360 and GSE97320 datasets, we screened shared differentially expressed genes (DEGs) in the independent datasets. Functional enrichment analysis and protein-protein interaction (PPI) network were employed. GSE58967 of 111 AMI patients and 46 controls was used to validate the shared DEGs and further analyzed to identify the DEGs in AMI patients with and without heart failure (HF) with the dynamic changes also being evaluated. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to validate the diagnostic efficiency. Results In the comparison of AMI patients with controls, we identified 105 shared DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the shared DEGs mainly enriched in immune-related inflammation process and pathways. Filtered with PPI network, 5 genes of CXCL8, CXCL1, MMP9, FPR1 and TLR2 were considered as hub genes, which were further validated in GSE59867. Compared with the genes in AMI patients without HF, those of TNFAIP6, ADM, TRIB1, AQP9 and IL1R2 associated with ventricular remodeling were found to be significantly high expressed in patients with HF on admission with the AUC of ROC curves was 0.792–0.847 (all p < 0.05), which can be used as the potential biomarkers for early prediction of HF after AMI. Conclusions These findings based on integrated bioinformatic analysis provide new insights into the important roles of genes to play in the patients with AMI and consequent HF.

Sign in / Sign up

Export Citation Format

Share Document