The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs

Abstract

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Síndrome metabólica, aterosclerose e inflamação: tríade indissociável?

“…The increases in fibrinogen, fibrin and products of fibrinogen degradation can lead to sclerosis of the vessel walls and to narrowing of the lumen, in addition to contributing to plaque rupture. [52][53][54] Another marker of inflammation is CD40, which is expressed by T lymphocytes and by activated platelets, in addition to being expressed by endothelial cells on the surfaces of smooth muscle cells and in macrophages. The soluble ligand of this marker, sCD40L, can also be found in the form of a transmembrane protein and elevated sCD40L levels can also be indicative of an increased risk of CVD.…”

“…This metalloproteinase activates MMP-2 and also regulates expression of IL-1b, IL-8, CD2, CD4, CD8 and TNF-α, aggravating inflammatory events. [54][55][56] In view of the above, it can be stated that inflammation plays an indispensable role in genesis and progression of atherosclerosis. Another important factor (already mentioned in connection with AGES) is NF-κB, which induces expression of several chemical mediators of inflammation, contributing to formation and development of atherosclerotic plaques.…”

“…Studies show that fibrinogen, fibrin and products of fibrinogen degradation can regulate the activity of MMP-2 and VEGF, by activation of PKC and MAPK via the influence of NF-κB. 54,[57][58][59] Several authors have shown an association between CRP and MS levels and indicators of atherosclerotic plaques. Higher plaque scores and greater thickness of the intima and media of vessels have been observed in people with MS.…”

The relation between increased carotid intima‐media thickness with fibrin monomers in obese children

“…Fibrin and fibrin degradation products are associated with increased risk of atherosclerosis. [36][37][38] However, the role of fibrin and fibrin degradation products in atherosclerosis plaque has not been enlightened completely. The relation between CIMT as the early indicator of atherosclerosis and fibrin monomers was investigated in animal studies and a few postmortem human studies.…”

Endothelial lipase is upregulated by interleukin-6 partly via the p38 MAPK and p65 NF-κB signaling pathways

“…The activation of NF-κB has also been observed in human and experimental atherosclerosis ( 31 , 32 ). Cao et al ( 33 ) found that the progression of the instability of atherosclerotic plaques may be mediated by the NF-κB pathway.…”