Actions of thrombin in the interstitium

Ridder, Gustaaf G. de; Lundblad, Roger L.; Pizzo, Salvatore V.

doi:10.1111/jth.13191

Cited by 12 publications

(10 citation statements)

References 93 publications

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“…47 Thrombin may also activate proteolytic enzymes that degrade interstitium and extracellular matrix. 48 Fibrinogen (and its polymerized version fibrin) may enter into the brain and limit tissue repair. 49 All these blood-derived molecules would maintain a neuro-inflammatory status that may contribute to brain cells death.…”

Section: Hypothetical Biological Cascades Following the Onset Of Cmbsmentioning

confidence: 99%

Cerebral microbleeds: Beyond the macroscope

Pétrault

Casolla

Ouk

et al. 2019

International Journal of Stroke

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While being increasingly recognized in clinical routine, brain microbleeds remain a puzzling finding for physicians. These small dot-like lesions are thought to be old perivascular collections of hemosiderin deposits. They can be found in different neurological settings such as cerebrovascular or neurodegenerative diseases. While their microscopic size would suggest considering these lesions as anecdotal, they are now regarded as biomarkers of severity of an underlying cerebrovascular disease. Their natural history and the interactions with surrounding brain cells remain unknown. However, their presence may impact therapeutic decisions. Deciphering the biological mechanisms leading to, or following microbleeds would enable us to address a key question: do microbleeds arise and impact the surrounding parenchyma like a miniature version of intracerebral hemorrhages or do they represent a different kind of injury? We hereby discuss, based on both clinical and experimental literature, the gap between the definition of microbleeds coming from neuroimaging and the pathophysiological hypotheses raised from histopathological and experimental data. Our analysis supports the need for a convergent effort from clinicians and basic scientists to go beyond the current “macro” view and disclose the cellular and molecular insights of these cerebral hemorrhagic microlesions.

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Section: Hypothetical Biological Cascades Following the Onset Of Cmbsmentioning

confidence: 99%

Cerebral microbleeds: Beyond the macroscope

Pétrault

Casolla

Ouk

et al. 2019

International Journal of Stroke

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“…Whether these latter processes initiate or maintain AF is still unknown. Nevertheless, it has been reported that coagulation plays a key role in fibrosis [81,82], although this has never been investigated in relation to AF. PAR1 and PAR2 are both expressed by cardiomyocytes, and are involved in the proliferation of embryotic cardiac fibroblasts [83], suggesting a possible role of thrombin in the onset of AF.…”

Section: Effects Of Inhibition Of Thrombin On Cardiovascular Pathophymentioning

confidence: 99%

Coagulation and non‐coagulation effects of thrombin

Posma

Posthuma

Spronk

2016

Journal of Thrombosis and Haemostasis

124

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To cite this article: Posma JJN, Posthuma JJ, Spronk HMH. Coagulation and non-coagulation effects of thrombin. J Thromb Haemost 2016; 14: 1908-16. Summary. Thrombin is a multifunctional serine protease produced from prothrombin, and is a key regulator in hemostatic and non-hemostatic processes. It is the main effector protease in primary hemostasis by activating platelets, and plays a key role in secondary hemostasis. Besides its well-known functions in hemostasis, thrombin also plays a role in various non-hemostatic biological and pathophysiologic processes, predominantly mediated through activation of protease-activated receptors (PARs). Depending on several factors, such as the concentration of thrombin, the duration of activation, the location of PARs, the presence of coreceptors, and the formation of PAR heterodimers, activation of the receptor by thrombin can induce different cellular responses. Moreover, thrombin can have opposing effects in the same cell; it can induce both inflammatory and antiinflammatory signals. Owing to the complexity of thrombin's signal transduction pathways, the exact mechanism behind the dichotomy of thrombin is yet still unknown. In this review, we highlight the hemostatic and non-hemostatic functions of thrombin, and specifically focus on the non-hemostatic dual role of thrombin under various conditions and in relation to cardiovascular disease.

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“…All these actions contribute to clot formation and maintenance. This enzyme yet has an anticoagulant function – thrombin activates protein C down-regulating the coagulation cascade [ 59 , 60 ].…”

Section: Enzyme Dysregulation Consequencesmentioning

confidence: 99%

The enzymes in COVID-19: A review

et al. 2022

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COVID-19 brought a scientific revolution since its emergence in Wuhan, China, in December 2019. Initially, the SARS-CoV-2 virus came to attention through its effects on the respiratory system. However, its actions in many other organs also have been discovered almost daily. As enzymes are indispensable to uncountable biochemical reactions in the human body, it is not surprising that some enzymes are of relevance to COVID-19 pathophysiology. Past evidence from SARS-CoV and MERS-CoV outbreaks provided hints about the role of enzymes in SARS-CoV-2 infection. In this setting, ACE-2 is an enzyme of great importance since it is the cell entry receptor for SARS-CoV-2. Clinical data elucidate patterns of enzymatic alterations in COVID-19, which could be associated with organ damage, prognosis, and clinical complications. Further, viral mutations can create new disease behaviors, and these effects are related to the activity of enzymes. This review will discuss the main enzymes related to COVID-19, summarizing the findings on their role in viral entry mechanism, the consequences of their dysregulation, and the effects of SARS-CoV-2 mutations on them.

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Actions of thrombin in the interstitium

Cited by 12 publications

References 93 publications

Cerebral microbleeds: Beyond the macroscope

Cerebral microbleeds: Beyond the macroscope

Coagulation and non‐coagulation effects of thrombin

The enzymes in COVID-19: A review

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