The Application of scRNA‐Seq in Heart Development and Regeneration DOI

Junying Gao,

Lindong Yu,

Haoran Qi

et al.

genesis, Journal Year: 2025, Volume and Issue: 63(2)

Published: April 1, 2025

ABSTRACT Single‐cell RNA sequencing (scRNA‐seq) is a rapidly developing and useful technique for elucidating biological mechanisms characterizing individual cells. Tens of millions patients worldwide suffer from heart injuries other types disease. Neonatal mammalian hearts certain adult vertebrate species, such as zebrafish, can fully regenerate after myocardial injury. However, the unable to damaged myocardium. scRNA‐seq provides many new insights into pathological normal facilitates our understanding cellular responses cardiac injury repair at different stages, which may provide critical clues effective therapies regeneration. In this review, we summarize application in development regeneration describe how important molecular be harnessed promote

Language: Английский

The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110–NF45 disassembly to promote heart regeneration in mice DOI
Wenya Ma,

Hongyang Chen,

Yanan Tian

et al.

Nature Cardiovascular Research, Journal Year: 2025, Volume and Issue: 4(1), P. 102 - 118

Published: Jan. 15, 2025

Language: Английский

Citations

4

Extracellular Matrix Interactome in Modulating Vascular Homeostasis and Remodeling DOI Open Access
Yi Fu, Yuan Zhou, Kai Wang

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 134(7), P. 931 - 949

Published: March 28, 2024

The ECM (extracellular matrix) is a major component of the vascular microenvironment that modulates homeostasis. proteins include collagens, elastin, noncollagen glycoproteins, and proteoglycans/glycosaminoglycans. form complex matrix structures, such as basal lamina collagen elastin fibers, through direct interactions or lysyl oxidase-mediated cross-linking. Moreover, directly interact with cell surface receptors extracellular secreted molecules, exerting matricellular matricrine modulation, respectively. In addition, proteases degrade cleave proteins, thereby contributing to turnover. These constitute interactome network, which essential for maintaining homeostasis preventing pathological remodeling. current review mainly focuses on endogenous in blood vessels discusses interaction these other receptors, cytokines, complement coagulation factors, their potential roles

Language: Английский

Citations

13

Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury DOI Creative Commons
Yihua Bei, Hongyun Wang, Yang Liu

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated the adaptation process induced by exercise; however, its impact on exercise-induced contribution to exercise-driven remain unclear. We investigated role mechanism of miR-210 explored whether contributes protection alleviating I/R Here, we first observed that regular swimming exercise markedly increase levels heart blood samples rats mice. Circulating were also elevated after a programmed rehabilitation patients diagnosed coronary diseases. In 8-week model wild-type (WT) knockout (KO) rats, demonstrated was not integral for hypertrophy but it did influence cardiomyocyte proliferative activity. neonatal rat cardiomyocytes, promoted cell proliferation suppressed apoptosis while altering size. Additionally, survival human embryonic stem cell-derived cardiomyocytes (hESC-CMs) AC16 line, indicating functional roles cardiomyocytes. further identified target genes, cyclin-dependent kinase 10 (CDK10) ephrin-A3 (EFNA3), regulate apoptosis. Finally, KO WT subjected followed crucially contributed against summary, this study elucidates miR-210, an exercise-responsive miRNA, promoting activity during growth. Furthermore, plays essential mediating protective effects Our findings suggest as potent nonpharmaceutical intervention inducing which alleviate injury promote cardioprotection.

Language: Английский

Citations

10

Cardiomyocyte senescence and the potential therapeutic role of senolytics in the heart DOI Open Access
Peiyong Zhai, Junichi Sadoshima

The Journal of Cardiovascular Aging, Journal Year: 2024, Volume and Issue: 4(2)

Published: June 3, 2024

Cellular senescence in cardiomyocytes, characterized by cell cycle arrest, resistance to apoptosis, and the senescence-associated secretory phenotype, occurs during aging response various stresses, such as hypoxia/reoxygenation, ischemia/reperfusion, myocardial infarction (MI), pressure overload, doxorubicin treatment, angiotensin II, diabetes, thoracic irradiation. Senescence heart has both beneficial detrimental effects. Premature of myofibroblasts salutary effects MI overload. On other hand, persistent activation cardiomyocytes precipitates cardiac dysfunction adverse remodeling through paracrine mechanisms MI, aging, doxorubicin-induced cardiomyopathy. Given roles many conditions, specific removal senescent cells, i.e., senolysis, is great interest. Senolysis can be achieved using senolytic drugs (such Navitoclax, Dasatinib, Quercetin), pharmacogenetic approaches (including INK-ATTAC AP20187, p16-3MR Ganciclovir, p16 ablation, p16-LOX-ATTAC Cre), immunogenetic interventions (CAR T cells or vaccination). In order enhance specificity decrease off-target approaches, investigation into which develop and/or maintain state needed.

Language: Английский

Citations

9

Targeting the E Prostanoid Receptor EP4 Mitigates Cardiac Fibrosis Induced by β‐Adrenergic Activation DOI Creative Commons
Hu Xu,

Xiuhui Mao,

Yali Wang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Sustained β-adrenergic activation induces cardiac fibrosis characterized by excessive deposition of extracellular matrix (ECM). Prostaglandin E2 (PGE2) receptor EP4 is essential for cardiovascular homeostasis. This study aims to investigate the roles cardiomyocyte (CM) and fibroblast (CF) in isoproterenol (ISO)-induced fibrosis. By crossing EP4f/f mice with α-MyHC-Cre or S100A4-Cre mice, this work obtains CM-EP4 knockout (EP4f/f-α-MyHCCre+) CF-EP4 (EP4f/f-S100A4Cre+) mice. The both genders are subcutaneously injected ISO (5 mg kg-1 day-1) 7 days. Compared control EP4f/f-α-MyHCCre+ EP4f/f-S100A4Cre+ show a significant improvement diastolic function as assessed echocardiography histological staining, respectively. In CMs, inhibition suppresses ISO-induced TGF-β1 expression via blocking cAMP/PKA pathway. CFs, reversed TGF-β1-triggers production ECM preventing formation TGF-β1/TGF-β complex blocks CF proliferation suppressing ERK1/2 Furthermore, double CM- administration antagonist, grapiprant, markedly improves dysfunction Collectively, demonstrates that contribute activation-induced Targeting may offer novel therapeutic approach

Language: Английский

Citations

1

The Role of the MAPK Signaling Pathway in Cardiovascular Disease: Pathophysiological Mechanisms and Clinical Therapy DOI Open Access
Xueyang Wang, Ruiqi Liu, Dan Liu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2667 - 2667

Published: March 16, 2025

Cardiovascular disease (CVD) is a serious global health issue with high mortality rates worldwide. Despite the numerous advancements in study of CVD pathogenesis recent years, further summarization and elaboration specific molecular pathways are required. An extensive body research has been conducted to elucidate association between MAPK signaling pathway, which present all eukaryotic organisms, cardiovascular disease. This review aims provide comprehensive summary on over past five years. The primary focus four diseases: heart failure, atherosclerosis, myocardial ischemia–reperfusion injury, cardiac hypertrophy. will also address pathophysiological mechanisms diseases, objective proposing novel clinical treatment strategies for CVD.

Language: Английский

Citations

1

KLF1 Promotes Cardiomyocyte Proliferation and Heart Regeneration Through Regulation of Wnt/β‐Catenin Signaling Pathway DOI Creative Commons

Yanglin Hao,

Feng Zhang, Shuan Ran

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Innovative therapeutic approaches for heart failure, a leading cause of mortality worldwide, are urgently needed. In this study, the important role Krüppel-like factor 1 (KLF1) in cardiomyocyte proliferation and regeneration is explored, revealed its ability to regulate Wnt/β-catenin signaling pathway as well exploring feasible strategy target KLF1 treatment failure. Postnatally, marked decrease expression occurred almost simultaneously with reduction myocardial regenerative capacity. Through comprehensive vivo vitro studies, it demonstrated that neonatal adult mice, overexpression significantly increased promoted repair following infarction, whereas knockout abolished these effects. Mechanistically, through RNA sequencing (RNA-seq) ATAC (ATAC-seq) analyses, promotion by associated pathway, mitochondrial function, fatty acid metabolism. These findings highlight regeneration, which provides novel insights into targets

Language: Английский

Citations

1

Myocardial fibrosis from the perspective of the extracellular matrix: mechanisms to clinical impact DOI
Ida G. Lunde, Karoline Bjarnesdatter Rypdal, Sophie Van Linthout

et al.

Matrix Biology, Journal Year: 2024, Volume and Issue: 134, P. 1 - 22

Published: Aug. 29, 2024

Language: Английский

Citations

7

Targeting cardiomyocyte cell cycle regulation in heart failure DOI Creative Commons
Chaonan Zhu, Ting Yuan, Jaya Krishnan

et al.

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: 119(3), P. 349 - 369

Published: April 29, 2024

Heart failure continues to be a significant global health concern, causing substantial morbidity and mortality. The limited ability of the adult heart regenerate has posed challenges in finding effective treatments for cardiac pathologies. While various medications surgical interventions have been used improve function, they are not able address extensive loss functioning cardiomyocytes that occurs during injury. As result, there is growing interest understanding how cell cycle regulated exploring potential stimulating cardiomyocyte proliferation as means promoting regeneration. This review aims provide an overview current knowledge on regulation mechanisms underlying cases failure, while also highlighting established novel therapeutic strategies targeting this area treatment purposes.

Language: Английский

Citations

5

Tudor-SN promotes cardiomyocyte proliferation and neonatal heart regeneration through regulating the phosphorylation of YAP DOI Creative Commons
Chao Su,

Jinzheng Ma,

Xuyang Yao

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 28, 2024

Abstract Background The neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose capacities. Therefore, investigating mechanisms underlying proliferation regeneration is crucial for unlocking of adult to repair damage restore contractile function myocardial injury. Methods Tudor staphylococcal nuclease ( Tudor-SN ) transgenic (TG) or cardiomyocyte-specific knockout mice Myh6-Tudor-SN −/− were generated investigate role in apical resection (AR) surgery. Primary isolated used assess influence on vitro. Affinity purification mass spectrometry employed elucidate mechanism. H9c2 cells mouse myocardia with either overexpression utilized its impact phosphorylation Yes-associated protein (YAP), both vitro vivo. Results We previously identified as a regulator that highly expressed but downregulated adults. Our present study demonstrates sustained expression promotes prolongs cardiomyocytes, improves cardiac function, enhances ability left ventricular apex mice. Consistently, impairs retards recovery after associates YAP, which plays important roles development regeneration, inhibiting at Ser 127 397 residues by preventing association between Large Tumor Suppressor 1 (LATS1) correspondingly maintaining stability promoting nuclear translocation YAP enhance proliferation-related genes transcription. Conclusion regulates consequently enhancing prolonging under physiological conditions Graphical

Language: Английский

Citations

5