Platelet-monocyte aggregates: molecular mediators of thromboinflammation

Rolling, Christina C.; Barrett, Tessa; Berger, Jeffrey S.

doi:10.3389/fcvm.2023.960398

Cited by 9 publications

(10 citation statements)

References 161 publications

(190 reference statements)

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“…Moreover, recent evidence has shown that monocytes are activated to have prothrombotic and proinflammatory features once binding with platelets in inflammatory and autoimmune disorders. Thus, monocyte‐platelet interactions serve as a key element connecting thrombosis and inflammation 54 . Taken together, thromboinflammation is likely to contribute to and exacerbate the microangiopathy and nerve degeneration of ATTRv.…”

Section: Discussionmentioning

confidence: 99%

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Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis

Yeh,

Wang

et al. 2023

Ann Clin Transl Neurol

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ObjectiveDespite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified.MethodsThis study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR‐A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC‐1) culture to examine the direct effect of TTR‐A97S protein on endothelial cells.ResultsIn ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC‐1 culture in which the expression of collagen IV was upregulated after exposure to TTR‐A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p‐selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv.InterpretationMicroangiopathy with thromboinflammation is characteristic of advanced‐stage ATTRv nerves, which provides an add‐on mechanism and therapeutic target for nerve degeneration.

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Section: Discussionmentioning

confidence: 99%

“…Thus, monocyte‐platelet interactions serve as a key element connecting thrombosis and inflammation. 54 Taken together, thromboinflammation is likely to contribute to and exacerbate the microangiopathy and nerve degeneration of ATTRv.…”

Section: Discussionmentioning

confidence: 99%

Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis

Yeh,

Wang

et al. 2023

Ann Clin Transl Neurol

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“…On monocytes, P-selectin binding rapidly exposes tissue factor (TF), the coagulation initiator, to the surface [ 29 , 30 , 31 , 32 , 33 , 34 ]. Over time, the expression of the TF gene increases and TF is released from the surface of monocytes in extracellular vesicles.…”

Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

“…These processes, along with platelet aggregation and fibrin deposition, can cause vascular occlusion even without physical injury to the blood vessels. Platelets also act as protectors by preventing bleeding On monocytes, P-selectin binding rapidly exposes tissue factor (TF), the coagulation initiator, to the surface [29][30][31][32][33][34]. Over time, the expression of the TF gene increases and TF is released from the surface of monocytes in extracellular vesicles.…”

Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

Nappi

2023

IJMS

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Thromboinflammation, the interplay between thrombosis and inflammation, is a significant pathway that drives cardiovascular and autoimmune diseases, as well as COVID-19. SARS-CoV-2 causes inflammation and blood clotting issues. Innate immune cells have emerged as key modulators of this process. Neutrophils, the most predominant white blood cells in humans, are strategically positioned to promote thromboinflammation. By releasing decondensed chromatin structures called neutrophil extracellular traps (NETs), neutrophils can initiate an organised cell death pathway. These structures are adorned with histones, cytoplasmic and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects that can hasten disease progression. Protein arginine deiminase 4 (PAD4) catalyses the citrullination of histones and is involved in the release of extracellular DNA (NETosis). The neutrophil inflammasome is also required for this process. Understanding the link between the immunological function of neutrophils and the procoagulant and proinflammatory activities of monocytes and platelets is important in understanding thromboinflammation. This text discusses how vascular blockages occur in thromboinflammation due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). The activity of PAD4 is important for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. This article reviews how vaso-occlusive events in thrombo-inflammation occur through the interaction of neutrophil extracellular traps with von Willebrand factor. It highlights the relevance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and cardiovascular disease. Interaction between platelets, VWF, NETs and inflammasomes is critical for the progression of thromboinflammation in several diseases and was recently shown to be active in COVID-19.

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“…On monocytes, P-selectin binding rapidly exposes tissue factor (TF), the coagulation initiator, to the surface. (29)(30)(31)(32)(33)(34) Over time, the expression of the TF gene increases and TF is released from the surface of monocytes in extracellular vesicles. The primary source of TF in the blood is then the activated monocyte.…”

Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

Atherosclerosis Progression and COVID 19: The Role of Tromboinflammation

Nappi

2023

Preprint

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The interplay between thrombosis and inflammation, known as thromboinflammation, is a significant pathway driving cardiovascular and autoimmune diseases, as well as COVID-19. Key modulators of this process have emerged as innate immune cells. Strategically positioned to promote thromboinflammation are neutrophils, the most predominant white blood cells in humans. Neutrophils can trigger an organized cell death pathway by releasing decondensed chromatin structures known as neutrophil extracellular traps. These structures are decorated with histones, cytoplasmic, and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects, which can accelerate disease progression. The activities of PAD4, which catalyses the citrullination of histones, and the neutrophil inflammasome are required for distinct steps leading to extracellular DNA release (NETosis). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. We will discuss how vascular blockages in thromboinflammation occur due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. It will also review the mechanisms whereby vaso-occlusive events in thrombo-inflammation depend on the interaction of neutrophil extracellular traps with von Willebrand factor and suggest the importance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and CVD.

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Platelet-monocyte aggregates: molecular mediators of thromboinflammation

Cited by 9 publications

References 161 publications

Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis

Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

Atherosclerosis Progression and COVID 19: The Role of Tromboinflammation

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