The multifaceted role of fibrinogen in tissue injury and inflammation

Abstract

The canonical role of the hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological end points of hemorrhage or thrombosis with vessel occlusion. However, fibrin(ogen) and proteases controlling its deposition and clearance, including (pro)thrombin and plasmin(ogen), have powerful roles in driving acute and reparative inflammatory pathways that affect the spectrum of tissue injury, remodeling, and repair. Indeed, fibrin(ogen) deposits are a near-universal feature of tissue injury, regardless of the nature of the inciting event, including injuries driven by mechanical insult, infection, or immunological derangements. Fibrin can modify multiple aspects of inflammatory cell function by engaging leukocytes through a variety of cellular receptors and mechanisms. Studies on the role of coagulation system activation and fibrin(ogen) deposition in models of inflammatory disease and tissue injury have revealed points of commonality, as well as context-dependent contributions of coagulation and fibrinolytic factors. However, there remains a critical need to define the precise temporal and spatial mechanisms by which fibrinogen-directed inflammatory events may dictate the severity of tissue injury and coordinate the remodeling and repair events essential to restore normal organ function. Current research trends suggest that future studies will give way to the identification of novel hemostatic factor-targeted therapies for a range of tissue injuries and disease.

Preoperative Serum Fibrinogen is Associated With Acute Kidney Injury after Cardiac Valve Replacement Surgery

“…In terms of the pathophysiology of cardiac surgery-associated AKI, one main factor for the development of AKI is inflammation 4 . Fibrinogen is also recognized as an acute-phase response protein, and it increases several-fold during inflammation or tissue damage 15 . Previous study has found that fibrinogen stimulates chemotactic cell migration on binding to the leukocyte integrin receptor 24 .…”

“…www.nature.com/scientificreports www.nature.com/scientificreports/ Regardless of the stimulating source or severity of the injury, almost all forms of tissue injury are associated with local activation of the coagulation system. Fibrinogen plays a key role in the acute phase response to tissue injury, where thrombin cleavage of fibrinogen integrates with the acute inflammatory response to inhibit tissue damage 15 . Therefore, preoperative serum fibrinogen may not simply reflect coagulation, but it may be a marker of multi-tissue damage.…”

“…Fibrinogen is recognized as an acute-phase response protein, and it increases several-fold during inflammation or tissue damage 15 . Several studies have found that serum or urinary fibrinogen is associated with contrast-induced nephropathy 16 and sepsis-associated AKI 17 .…”

Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel

“…For example, P‐selectin binds to P‐selectin glycoprotein ligand‐1 on monocytes, leading to production and exposure of tissue factor (TF) on monocytes and secretion of pro‐inflammatory cytokines . Fibrinogen binds both to the CD11b/CD18 receptor (Mac‐1) on monocytes, thereby activating monocytes, and to the activated GPIIb/IIIa, thereby enabling platelet aggregation . Altogether, EVs exposing PS, P‐selectin, and/or fibrinogen may (a) contribute to thrombus formation, and (b) be involved in maintaining the chronic inflammatory state of the vessel wall after AMI.…”

Spike protein up-regulates inflammatory axis of both thromboinflammation and leukotriene in severe COVID-19

“…As one of the most potent in ammatory mediators, brinogen has powerful role in driving in ammatory responses and can be up-regulated by virus infection [10][11][12] . As illustrated in Figure 1A and Table S1 and 2, blood routine examination showed that mean plasma brinogen concentration in ICU (4.868 mg/ml) (S-SC, n = 22; male 12; female 10; age: 36-77 years) and in non-ICU (4.109 mg/ml) patients (MM, n = 40; male 20; female 20; age: 10-73 years) was much higher than that in control healthy (2.903 mg/ml) (HC, n = 37; male 19; female 18; age: 28-56 years).…”