Fibrinogen and Atherosclerotic Cardiovascular Diseases-Review of the Literature and Clinical Studies

Abstract

Atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral arterial disease, represent a significant cause of premature death worldwide. Biomarkers, the evaluation of which would allow the detection of ASCVD at the earliest stage of development, are intensively sought. Moreover, from a clinical point of view, a valuable biomarker should also enable the assessment of the patient's prognosis. It has been known for many years that the concentration of fibrinogen in plasma increases, inter alia, in patients with ASCVD. On the one hand, an increased plasma fibrinogen concentration may be the cause of the development of atherosclerotic lesions (increased risk of atherothrombosis); on the other hand, it may be a biomarker of ASCVD, as it is an acute phase protein. In addition, a number of genetic polymorphisms and post-translational modifications of fibrinogen were demonstrated that may contribute to the risk of ASCVD. This review summarizes the current data on the importance of fibrinogen as a biomarker of ASCVD, and also presents the relationship between molecular modifications of this protein in the context of ASCVD.

Keywords: atherosclerosis; atherosclerotic cardiovascular disease; fibrinogen.

Figure 1

Fibrinogen biosynthesis in liver hepatocytes [9,10,11]. DNA—deoxyribonucleic acid; mRNA—Messenger ribonucleic acid; FGA-FGB-FGG—Fibrinogen chain genes; miRNA—Micro RNA; HNF4α—Hepatocyte Nuclear Factor 4 Alpha; HNF1—Hepatocyte nuclear factor 1; C/EBP—CCAAT enhancer binding proteins; IL-6RE—IL-6 response element; SOCS3—Suppressor of cytokine signaling 3; miR-18a—microRNA-18a; NFκB—Nuclear factor kappa-light-chain-enhancer of activated B cells; PIAS3—Protein inhibitor of activated STAT 3; STAT3—Signal transducer and activator of transcription 3; HNF3—Hepatocyte nuclear factor 3; IL-1β—Interleukin 1β, IL-6—Interleukin 6; GR—Glucocorticoid receptor; GC—Glucocorticosteroids; Bβ, Aα and γ—Fibrinogen polypeptide chains.

Figure 2

The role of fibrinogen in blood coagulation [21]. TF—Tissue factor, GP IIb/IIIa—Integrin receptors.

Figure 3

Alternative FGG pre-mRNA processing [67,68,69]. The γA chain arises when polyadenylation occurs at polyadenylation signal 2 (pA2) downstream of exon 10, and all 9 introns are removed. The alternative chain arises after polyadenylation at pA1 in intron 9. This leads to the translation of a polypeptide with a unique 20-amino acid extension encoded by intron 9, substituting the 4 γA amino acids of exon 10.