Thrombospondin 1 and Reelin act through Vldlr to regulate cardiac growth and repair

Pei, Lijuan; Ouyang, Zhaohui; Zhang, Hongjie; Huang, Shiqi; Jiang, Rui; Liu, Bilin; Tang, Yansong; Feng, Mengying; Yuan, Min; Wang, Haocun; Yao, Su; Shi, Shuyue; Yu, Zhao; Xu, Dachun; Gong, Guohua; Wei, Ke

doi:10.1007/s00395-023-01021-1

Cited by 2 publications

(2 citation statements)

References 77 publications

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“…Wang et al showed that after MI, the transcription factor Tbx1, which attracts tDCs, Tregs, and reparative macrophages via chemokine Ccl21 and integrin Icam1, is upregulated in cardiac lymphatic ECs, promoting an immunosuppressive microenvironment for cardiomyocyte regeneration ( Wang W. et al, 2023 ). Recently, Wei et al reported that the Reelin and TSP-1 signals, which have opposing effects on CM proliferation, simultaneously act on the VLDLR receptor on CMs, with Rac1 and YAP serving as downstream ( Pei et al, 2023 ). The restoration of blood supply following injury is a pivotal process for cardiac regeneration ( Mathison and Rosengart, 2018 ).…”

Section: The Extracellular Microenvironment Of Cardiomyocytes Favors ...mentioning

confidence: 99%

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

Zheng,

Hao,

Xia

et al. 2024

Front. Cell Dev. Biol.

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The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.

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Section: The Extracellular Microenvironment Of Cardiomyocytes Favors ...mentioning

confidence: 99%

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

Zheng,

Hao,

Xia

et al. 2024

Front. Cell Dev. Biol.

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“…Reelin is also abundant in the blood with a typical concentration of around 10 ng/mL in humans [53], and exercises function outside of the CNS [51,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71]. In the past 10 years, three major non-neuronal functions for plasma Reelin have been described in inflammation, vascular tone regulation, and thrombosis.…”

Section: Introductionmentioning

confidence: 99%

Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases

Calvier,

Alexander,

Marckx

et al. 2024

Cells

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Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial–leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases. We found that Reelin expression remains stable throughout adulthood and that peripheral anti-Reelin antibody treatment with CR-50 efficiently depletes plasma Reelin without affecting its levels or functionality within the CNS. Notably, this approach preserves essential neuronal functions and synaptic plasticity. Furthermore, in mice induced with experimental autoimmune encephalomyelitis (EAE), selective modulation of endothelial responses by anti-Reelin antibodies reduces pathological leukocyte infiltration without completely abolishing diapedesis. Finally, long-term Reelin depletion under metabolic stress induced by a Western diet did not negatively impact the heart, kidney, or liver, suggesting a favorable safety profile. These findings underscore the promising role of peripheral anti-Reelin therapeutic strategies for autoimmune diseases and conditions where endothelial function is compromised, offering a novel approach that may avoid the immunosuppressive side effects associated with conventional anti-inflammatory therapies.

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Thrombospondin 1 and Reelin act through Vldlr to regulate cardiac growth and repair

Cited by 2 publications

References 77 publications

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration

Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases

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