Hippo signaling in cardiac fibroblasts during development, tissue repair, and fibrosis

Tsai, Chang-Ru; Martin, James F.

doi:10.1016/bs.ctdb.2022.02.010

Cited by 8 publications

(9 citation statements)

References 140 publications

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“…The HS pathway is known to play key roles in regulating organ size, tissue repair, vascular remodeling cell proliferation, and apoptosis 103–106 . Dysregulation of HS can lead to cardiomyopathies, cardiac dysfunction, fibrosis, and heart failure 107–110 .…”

Section: Discussionmentioning

confidence: 99%

“…The HS pathway is known to play key roles in regulating organ size, tissue repair, vascular remodeling cell proliferation, and apoptosis. [103][104][105][106] Dysregulation of HS can lead to cardiomyopathies, cardiac dysfunction, fibrosis, and heart failure. [107][108][109][110] As such, HS is under strict control to maintain a proper balance of cell renewal and cell death to regulate cardiac remodeling and tissue homeostasis.…”

Section: Hs Pathwaymentioning

confidence: 99%

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Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

et al. 2023

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The marsupial Monito del monte (Dromiciops gliroides) utilizes both daily and seasonal bouts of torpor to preserve energy and prolong survival during periods of cold and unpredictable food availability. Torpor involves changes in cellular metabolism, including specific changes to gene expression that is coordinated in part, by the posttranscriptional gene silencing activity of microRNAs (miRNA). Previously, differential miRNA expression has been identified in D. gliroides liver and skeletal muscle; however, miRNAs in the heart of Monito del monte remained unstudied. In this study, the expression of 82 miRNAs was assessed in the hearts of active and torpid D. gliroides, finding that 14 were significantly differentially expressed during torpor. These 14 miRNAs were then used in bioinformatic analyses to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were predicted to be most affected by these differentially expressed miRNAs. Overexpressed miRNAs were predicted to primarily regulate glycosaminoglycan biosynthesis, along with various signaling pathways such as Phosphoinositide‐3‐kinase/protein kinase B and transforming growth factor‐β. Similarly, signaling pathways including phosphatidylinositol and Hippo were predicted to be regulated by the underexpression of miRNAs during torpor. Together, these results suggest potential molecular adaptations that protect against irreversible tissue damage and enable continued cardiac and vascular function despite hypothermia and limited organ perfusion during torpor.

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Section: Discussionmentioning

confidence: 99%

Section: Hs Pathwaymentioning

confidence: 99%

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

et al. 2023

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“…An ancient organ size control pathway (Hippo signaling) specifically inhibits cardiomyocyte proliferation in the adult heart [ 48 , 49 ]. Regulating the balance between cell differentiation, proliferation, and apoptosis, the Hippo signaling pathway also governs cardiac fibroblasts’ function and, subsequently, heart fibrosis [ 50 ], together with the endothelial response to oxidative stress, inflammation, and angiogenesis [ 51 ]. For these reasons, the inactivation of the Hippo pathway has been proposed as part of the putative strategies to promote myocardial regeneration after an injury [ 52 ].…”

Section: Bedside: Caveats From Clinical Experiencementioning

confidence: 99%

Pulmonary Artery Banding for Dilated Cardiomyopathy in Children: Returning to the Bench from Bedside

2022

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Current treatment paradigms for end-stage dilated cardiomyopathy (DCM) in children include heart transplantation and mechanical support devices. However, waitlist mortality, shortage of smaller donors, time-limited durability of grafts, and thrombo-hemorrhagic events affect long-term outcomes. Moreover, both these options are noncurative and cannot preserve the native heart function. Pulmonary artery banding (PAB) has been reinvented as a possible “regenerative surgery” to retrain the decompensated left ventricle in children with DCM. The rationale is to promote positive ventricular–ventricular interactions that result in recovery of left ventricular function in one out of two children, allowing transplantation delisting. Although promising, global experience with this technique is still limited, and several surgical centers are reluctant to adopt PAB since its exact biological bases remain unknown. In the present review, we summarize the clinical, functional, and molecular known and supposed working mechanisms of PAB in children with DCM. From its proven efficacy in the clinical setting, we described the macroscopic geometrical and functional changes in biventricular performance promoted by PAB. We finally speculated on the possible underlying molecular pathways recruited by PAB. An evidence-based explanation of the working mechanisms of PAB is still awaited to support wider adoption of this surgical option for pediatric heart failure.

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“…YAP has been shown to bind to the Ccl2 promoter in cardiac broblasts, whereas YAP overexpression promotes the expression of in ammationrelated genes. Therefore, the pharmacological inhibition of Hippo signaling is considered an effective strategy for promoting recovery from heart failure [14]. Moreover, the pharmacological inhibition of Hippo signaling could be an effective strategy to combat heart failure.…”

Section: Introductionmentioning

confidence: 99%

Verteporfin attenuates cardiac fibrosis after myocardial infarction by suppressing the YAP-Smad2/3 signaling pathway

Zhang

Liao

Gan

et al. 2023

Preprint

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Purpose Excessive cardiac fibrosis and remodeling occur after myocardial infarction. Yes-associated protein (YAP) is a major transcriptional co-activator of the Hippo pathway and an important regulator of cardiac fibrosis. Verteporfin is a pharmacological inhibitor of YAP that effectively inhibits fibrosis and inflammatory responses. Therefore, this study aimed to explore the effects of verteporfin on cardiac fibrosis after myocardial infarction (MI) and its possible mechanisms. Methods Wild-type C57BL/6J mice were subjected to MI by ligating their left anterior descending coronary artery (LAD) and treating them with verteporfin (50 mg/kg/48 h) or phosphate-buffered saline for 2 weeks. Echocardiography was performed to evaluate cardiac function after 2 weeks, and hematoxylin and eosin and Masson staining were performed to evaluate the degree of myocardial fibrosis and inflammatory response. The protein expression levels of the YAP-Smad2/3 pathway, inflammatory factors, and fibrosis markers in the heart and in vitro were determined using western blotting and immunofluorescence staining. Results Compared to the MI group, verteporfin treatment improved cardiac function and fibrosis in mice post-MI. Moreover, myocardial YAP and SMAD2/3 expression were reduced in verteporfin-treated animals. Hematoxylin and eosin staining and molecular examination showed inflammatory factor and cardiac fibrosis marker expression in the heart sections. Conclusion Verteporfin can attenuate cardiac fibrosis and inflammatory responses and improve cardiac function by suppressing the YAP-Smad2/3 signaling pathway post-MI.

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Hippo signaling in cardiac fibroblasts during development, tissue repair, and fibrosis

Cited by 8 publications

References 140 publications

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

Pulmonary Artery Banding for Dilated Cardiomyopathy in Children: Returning to the Bench from Bedside

Verteporfin attenuates cardiac fibrosis after myocardial infarction by suppressing the YAP-Smad2/3 signaling pathway

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