Altered plasma fibrin clot properties in hypertensive patients with obstructive sleep apnoea are improved by continuous positive airway pressure treatment

Jozwik-Plebanek, K.; Prejbisz, Aleksander; Wypasek, Ewa; Pręgowska−Chwała, Barbara; Kaszuba, Anna M.; Januszewicz, Magdalena; Bieleń, Przemysław; Kabat, Marek; Kruk, Mariusz; Dobrowolski, Piotr; Klisiewicz, Anna; Śliwiński, Paweł; Januszewicz, Andrzej; Undas, Anetta

doi:10.1097/hjh.0000000000001269

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…Moreover, γ' fibrinogen -originating from alternative mRNA processingwas not analyzed. Indeed, higher plasma concentrations of γ' fibrinogen yield fibrinolysis-resistant thrombi [45,46]. Another limitation of our study includes the lack of direct functional experiments demonstrating the role of IL-6 in leukocyte redox abnormalities.…”

Section: Discussionmentioning

confidence: 99%

ROS-driven structural and functional fibrinogen modifications are reverted by interleukin-6 inhibition in Giant Cell Arteritis

Bettiol,

Argento,

Fini

et al. 2023

Thrombosis Research

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Section: Discussionmentioning

confidence: 99%

ROS-driven structural and functional fibrinogen modifications are reverted by interleukin-6 inhibition in Giant Cell Arteritis

Bettiol,

Argento,

Fini

et al. 2023

Thrombosis Research

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“…Consistent with studies in healthy human plasma, the fibrin clot structure formed ex vivo in plasma derived from endotoxemic mice treated with the A2 protein also demonstrated increased porosity, compared with corresponding sick animals with mutant A2. It has been reported that changes in the architecture of the fibrin clot are associated with a high risk for thrombosis in certain diseases, 7,9,10,[35][36][37] and several studies have indicated that an increase in fibrin network porosity facilitates fibrinolysis. [38][39][40] Such a potential mechanistic effect of the A2 protein is consistent with the observation that microvascular thrombosis as well as widespread fibrin deposition in kidneys was markedly reduced in the A2-treated endotoxemic sick mice.…”

Section: Discussionmentioning

confidence: 99%

“…It is well appreciated that alterations in the fibrin clot profile are directly associated with different clinical pathologies, including conditions associated with bleeding and thrombosis. [7][8][9][10][11][12] Therefore, the development of interventions to modify fibrin clot structure and stability to prevent pathologic hemorrhage and thrombosis in systemic inflammation is an unmet medical need.…”

Section: Introductionmentioning

confidence: 99%

Modulating the rate of fibrin formation and clot structure attenuates microvascular thrombosis in systemic inflammation

et al. 2020

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Systemic inflammation can lead to coagulopathy and disseminated intravascular coagulation (DIC). In prior studies, the recombinant A2 domain of human von Willebrand factor (VWF; A2 protein) attenuated DIC and decreased mortality in lipopolysaccharide (LPS)-treated mice. Here, we performed studies to dissect the mechanism by which the A2 protein moderates DIC. We used confocal microscopy to analyze the fibrin clot structure in plasma from healthy humans and endotoxemic mice, turbidity assays to examine fibrin polymerization, and a murine model for LPS-induced DIC and introduced a loss-of-function mutation into the A2 protein for fibrin. The mutation of the residue E1567 located in the α2 helix of the folded A2 domain of VWF inhibited binding activity for fibrin, possibly mapping a novel region containing a putative binding site for fibrin. The A2 protein increased the initial rate of change of fibrin polymerization, intercalated into the fibrin network, and modified the resultant clot structure in vitro. Furthermore, ex vivo experiments using plasma from mice with endotoxemia treated with the A2 protein revealed an increased rate of fibrin formation and an altered clot structure as compared with plasma from nontreated sick animals. Moreover, and in contrast to the A2 mutant, the A2 protein improved survival and reduced fibrin deposition and microvascular thrombosis in mice with endotoxemia-induced DIC. Importantly, in vivo and in vitro studies indicated that the A2 protein did not affect experimental thrombosis. Thus, we provide evidence for a novel treatment to attenuate systemic inflammation-induced coagulopathy/DIC via targeting fibrin formation, without an increased risk for bleeding.

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“…OSA patients are characterized by elevated plasma fibrinogen levels which is induced by chronic inflammation, exaggerated platelet activity, and reduced fibrinolytic capacity. In hypertensive patients with OSA fibrin clot was characterized by more compact fibrin structure, impaired fibrinolysis and faster clot formation, which was normalized after 3 months of CPAP treatment [ 109 ].…”

Section: Platelet Functionmentioning

confidence: 99%

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

Mochol

Gawryś

Gajecki

et al. 2021

IJMS

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Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke.

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Altered plasma fibrin clot properties in hypertensive patients with obstructive sleep apnoea are improved by continuous positive airway pressure treatment

Abstract: In hypertensive patients at high cardiovascular risk, OSA was associated with unfavourable prothrombotic fibrin clot characteristics, including hypofibrinolysis, which significantly improve as early as after 3 months of CPAP treatment.

Cited by 10 publications

References 31 publications

ROS-driven structural and functional fibrinogen modifications are reverted by interleukin-6 inhibition in Giant Cell Arteritis

ROS-driven structural and functional fibrinogen modifications are reverted by interleukin-6 inhibition in Giant Cell Arteritis

Modulating the rate of fibrin formation and clot structure attenuates microvascular thrombosis in systemic inflammation

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

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