Therapeutic effect of SP‐8356 on pulmonary embolism‐associated cardiac injury is mediated by its ability to suppress apoptosis and inflammation

Jia, Zhiyuan; Li, Kai; Cheng, Feng; Peng, Zhengliang; Luo, Wei

doi:10.1111/jcmm.16535

Cited by 2 publications

(4 citation statements)

References 23 publications

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“…MMP-9 is a crucial member of the matrix metalloproteinase family, which is implicated in airway remodeling and induces mesenchymal cell proliferation and alveolar epithelial damage, resulting in lung function impairment ( Pardo et al, 2016 ). Zhou et al (2021) found increased MMP-9 protein expression in cardiomyocytes of rats with pulmonary embolism, similar to our results. Additionally, a recent study revealed increased VCAM-1-mediated vascular inflammation in a mouse model of acute lung diseases ( Kim et al, 2023 ).…”

Section: Discussionsupporting

confidence: 92%

“…P65 could regulate the transcription of various genes involved in the immune response, including cytokines and inflammatory mediators ( Zhao et al, 2020 ). Expression of p-ERK1/2 and p-P65/P65 was founded elevated in cardiomyocytes of rats with pulmonary embolism ( Zhou et al, 2021 ), consistent with our findings. In our study, R-hirudin attenuated p-ERK1/2/ERK1/2 and p-P65/P65 expression in lung tissues of APE rats in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 91%

“…In addition, significant oxidative stress occurred in APE patients, as evidenced by significantly elevated malondialdehyde (MDA), reactive oxygen species (ROS), and myeloperoxidase (MPO) levels ( Mühl et al, 2006 ). Increased matrix metalloproteinase-9 (MMP9), p-extracellular signal-regulated kinase (ERK)1/2, and p-P65 protein expression were also found in APE cell and rat models ( Zhou et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Wei,

Zou,

Dong

et al. 2024

PeerJ

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Background Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Wei,

Zou,

Dong

et al. 2024

PeerJ

View full text Add to dashboard Cite

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“…DAMP-induced damage can, in turn, generate DAMPs and precipitate self-perpetuating physiologic disarray in injured patients. A variety of potential pharmacological therapeutics exist with the potential to arrest these DAMP-related pathophysiological processes in trauma [ 54 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

Krocker

Lee

Henriksen

et al. 2022

IJMS

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Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. Conclusions: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.

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Therapeutic effect of SP‐8356 on pulmonary embolism‐associated cardiac injury is mediated by its ability to suppress apoptosis and inflammation

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 2 publications

References 23 publications

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

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