Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2

Vieceli Dalla Sega, Francesco; Fortini, Francesca; Licastro, Danilo; Monego, Simeone Dal; Degasperi, Margherita; Ascierto, Alessia; Marracino, Luisa; Severi, Paolo; D’Accolti, Maria; Soffritti, Irene; Brambilla, Marta; Camera, Marina; Tremoli, Elena; Contoli, Marco; Spadaro, Savino; Campo, Gianluca; Ferrari, Roberto; Caselli, Elisabetta; Rizzo, Paola

doi:10.1007/s00011-023-01823-y

Inflamm. Res.

2023

DOI: 10.1007/s00011-023-01823-y

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Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2

Francesco Vieceli Dalla Sega,

Francesca Fortini,

Danilo Licastro

et al.

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Cited by 4 publications

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ErbB2‐NOTCH1 axis controls autophagy in cardiac cells

Fortini,

Vieceli Dalla Sega,

Lazzarini

et al. 2024

BioFactors

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Although the epidermal growth factor receptor 2 (ErbB2) and Notch1 signaling pathways have both significant roles in regulating cardiac biology, their interplay in the heart remains poorly investigated. Here, we present evidence of a crosstalk between ErbB2 and Notch1 in cardiac cells, with effects on autophagy and proliferation. Overexpression of ErbB2 in H9c2 cardiomyoblasts induced Notch1 activation in a post‐transcriptional, p38‐dependent manner, while ErbB2 inhibition with the specific inhibitor, lapatinib, reduced Notch1 activation. Moreover, incubation of H9c2 cells with lapatinib resulted in stalled autophagic flux and decreased proliferation, consistent with the established cardiotoxicity of this and other ErbB2‐targeting drugs. Confirming the findings in H9c2 cells, exposure of primary neonatal mouse cardiomyocytes to exogenous neuregulin‐1, which engages ErbB2, stimulated proliferation, and this effect was abrogated by concomitant inhibition of the enzyme responsible for Notch1 activation. Furthermore, the hearts of transgenic mice specifically overexpressing ErbB2 in cardiomyocytes had increased levels of active Notch1 and of Notch‐related genes. These data expand the knowledge of ErbB2 and Notch1 functions in the heart and may allow better understanding the mechanisms of the cardiotoxicity of ErbB2‐targeting cancer treatments.

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ErbB2‐NOTCH1 axis controls autophagy in cardiac cells

Fortini,

Vieceli Dalla Sega,

Lazzarini

et al. 2024

BioFactors

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17β-estradiol inhibits Notch1 activation in murine macrophage cell line RAW 264.7

Severi,

Ascierto,

Marracino

et al. 2024

Mol Biol Rep

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Risks of major arterial and venous thrombotic diseases after hospitalisation for influenza, pneumonia, and COVID-19: A population-wide cohort in 2.6 million people in Wales

Keene,

Abbasizanjani,

Torabi

et al. 2025

Thrombosis Research

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Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2

Cited by 4 publications

References 72 publications

ErbB2‐NOTCH1 axis controls autophagy in cardiac cells

ErbB2‐NOTCH1 axis controls autophagy in cardiac cells

17β-estradiol inhibits Notch1 activation in murine macrophage cell line RAW 264.7

Risks of major arterial and venous thrombotic diseases after hospitalisation for influenza, pneumonia, and COVID-19: A population-wide cohort in 2.6 million people in Wales

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