Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Isshiki, Takuma; Sakamoto, Susumu; Homma, Sakae

doi:10.3390/medicina55050172

Cited by 8 publications

(3 citation statements)

References 103 publications

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“…HMGB1 also contributes to coagulation, as depicted by the platelets' aggregation upon the ligation of RAGE, platelet activation and thrombus formation due to HMGB1/TLR-4 signaling and the enhanced expression of tissue factor in monocytes and endothelial cells [57]. Intriguingly, during an early brain injury after SAH, there is also evidence of microvasospasms and microthrombosis and the degree of arteriolar constriction correlates with microthrombotic frequency [58].…”

Section: Discussionmentioning

confidence: 99%

Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

Muhammad

Chaudhry

Kahlert

et al. 2020

IJMS

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Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for “subarachnoid hemorrhage” in combination with “HMGB1”. Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.

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Section: Discussionmentioning

confidence: 99%

Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

Muhammad

Chaudhry

Kahlert

et al. 2020

IJMS

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“…Recombinant thrombomodulin (rhTM) has been investigated as a potential treatment in many pathologies, including sepsis (184,185), heat stroke (186), lung disease (187), disseminated intravascular coagulopathy (188), and autoimmune diseases (189,190). Given the diverse mechanisms of TM, clinical rhTM use has been trialed internationally for sepsis treatment (184,185).…”

Section: Othersmentioning

confidence: 99%

The neuro-endothelial axis in traumatic brain injury: mechanisms of multi-organ dysfunction, novel therapies, and future directions

Ho,

Dawood,

Taylor

et al. 2024

Shock

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Severe traumatic brain injury (TBI) often initiates a systemic inflammatory response syndrome (SIRS), which can potentially culminate into multi-organ dysfunction (MOD). A central player in this cascade is endotheliopathy, caused by perturbations in homeostatic mechanisms governed by endothelial cells due to injury-induced coagulopathy, heightened sympathoadrenal response, complement activation, and pro-inflammatory cytokine release. Unique to TBI is the potential disruption of the blood-brain barrier (BBB), which may expose neuronal antigens to the peripheral immune system and permit neuroinflammatory mediators to enter systemic circulation, propagating endotheliopathy systemically. This review aims to provide comprehensive insights into the “neuro-endothelial axis” underlying endothelial dysfunction following TBI, identify potential diagnostic and prognostic biomarkers, and explore therapeutic strategies targeting these interactions, with the ultimate goal of improving patient outcomes following severe TBI.

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“…This gene encodes an endothelial-specific type I membrane receptor that binds thrombin. CD141 is essential in the regulation of blood coagulation and inflammation [40,43]. Canonical EC MCAM Melanoma cell adhesion molecule MCAM is involved in vascular wound healing and acts upstream of or within angiogenesis [40].…”

Section: Cd141 Thrombomodulinmentioning

confidence: 99%

The Intersection of HIV and Pulmonary Vascular Health: From HIV Evolution to Vascular Cell Types to Disease Mechanisms

Garcia,

Almodovar

2024

JVD

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People living with HIV (PLWH) face a growing burden of chronic diseases, owing to the combinations of aging, environmental triggers, lifestyle choices, and virus-induced chronic inflammation. The rising incidence of pulmonary vascular diseases represents a major concern for PLWH. The study of HIV-associated pulmonary vascular complications ideally requires a strong understanding of pulmonary vascular cell biology and HIV pathogenesis at the molecular level for effective applications in infectious diseases and vascular medicine. Active HIV infection and/or HIV proteins disturb the delicate balance between vascular tone and constriction, which is pivotal for maintaining pulmonary vascular health. One of the defining features of HIV is its high genetic diversity owing to several factors including its high mutation rate, recombination between viral strains, immune selective pressures, or even geographical factors. The intrinsic HIV genetic diversity has several important implications for pathogenic outcomes of infection and the overall battle to combat HIV. Challenges in the field present themselves from two sides of the same coin: those imposed by the virus itself and those stemming from the host. The field may be advanced by further developing in vivo and in vitro models that are well described for both pulmonary vascular diseases and HIV for mechanistic studies. In essence, the study of HIV-associated pulmonary vascular complications requires a multidisciplinary approach, drawing upon insights from both infectious diseases and vascular medicine. In this review article, we discuss the fundamentals of HIV virology and their impact on pulmonary disease, aiming to enhance the understanding of either area or both simultaneously. Bridging the gap between preclinical research findings and clinical practice is essential for improving patient care. Addressing these knowledge gaps requires interdisciplinary collaborations, innovative research approaches, and dedicated efforts to prioritize HIV-related pulmonary complications on the global research agenda.

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Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Cited by 8 publications

References 103 publications

Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

The neuro-endothelial axis in traumatic brain injury: mechanisms of multi-organ dysfunction, novel therapies, and future directions

The Intersection of HIV and Pulmonary Vascular Health: From HIV Evolution to Vascular Cell Types to Disease Mechanisms

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