NF-κB — A Key Factor in Atherogenesis and Atheroprogression

Abstract

Atherosclerosis is the major cause of cardiovascular diseases and it is responsible for a large proportion of mortality in the Western society.Initially, atherosclerosis was thought to be a degenerative disease that was an inevitable consequence of aging. The recent research has shown that atherosclerosis is a slowly progressing inflammatory disease of the medium-and large-sized arteries, resulting in the formation of fatty and fibrous lesions.Inflammatory processes mark all stages of atherogenesis: from early endothelial activation by modified lipids to eventual rupture of the atherosclerotic plaque. The inflammation of the vessel wall is a feature of this pathology, which is characterized by infiltration and oxidation of low-density lipoproteins (LDLs), increase in oxidative stress, with the consequent lipid accumulation in the vessel wall, and foam cells formation.The extensive relation between the immune system and vessels induce the infiltration of immune cells into the vascular wall, the major pathogenic step in atherogenesis. At this aim, reactive oxygen species play a crucial role activating a number of redox-sensitive transcriptional factors such as nuclear factor kappa B (NF-κB), which is involved in transcription of many genes with an established role in atherosclerosis, such as cytokines, chemokines, adhesion molecules, acute phase proteins, regulators of apoptosis, and cell proliferation. Since its discovery in 1986, the transcription factor NF-κB has evoked large attention on the basis of its peculiar regulation, the abundance of activation stimuli, the different genes and biological responses controlled, the striking evolutionary conservation of structure and function among family members, and its role in different human diseases.Recognition of the leading role of inflammation at all stages of pathogenesis focuses on the potential relationship between systemic inflammation and atherosclerosis and fuelled intense basic science, health, and clinical research.The understanding of the inflammation involvement in atherogenesis, atheroprogression, and its complications confirm the importance of traditional risk factors in this disease, such as high LDL levels. Indeed, inflammatory process can be considered a pathway that, from mechanistic and functional points of view, suggests a connection with the known risk factors and alterations to the vessel biology that drive to atheroprogression and its complications.In this review, we discuss the transcription factor NF-κB and its potential role in atherogenesis and atheroprogression focusing on the major atherosclerotic factors regulated by NF-κB and how they may affect different steps in the atherosclerotic process.

Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response

“…Numerous reports have emphasized an important role of NFκB in the pathogenesis of various diseases that, on the one hand, are followed with the LGSIP development, e. g. metabolic syndrome [ 65 , 66 ], atherosclerosis [ 67 ], diabetes mellitus type 2 [ 68 ], osteoporosis [ 69 ], rheumatoid arthritis [ 70 ], inflammatory bowel diseases [ 71 ], multiple sclerosis and autoimmune encephalomyelitis [ 72 ], asthma and chronic obstructive pulmonary disease [ 73 ], periodontal disease [ 62 ], post-traumatic stress disorder [ 74 ], etc. But on the other, researchers point out a role of the NFκB activation in the mechanisms of diseases followed by the HGSIP development, in particular, septic shock [ 75 ], DIC [ 76 ], traumatic brain injury [ 77 ], burn injury [ 78 ], cytokine storming under COVID-19 [ 79 ].…”

The Effect Of Selenium Supplementation On The Expression Of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) And Malondialdehyde (MDA) In Wistar Rats Fed An Atherogenic Diet

“…Cellular aging is a risk factor for various aging-related diseases, such as cardiovascular disease, which is a significant cause of disability and premature death globally. A systematic review and meta-analysis study stated that globally in 2020, there was an increase in the prevalence of carotid artery thickening by 27.6%, and the percentage changed by 57.46% from 2000 (Bonomini et al, 2015;Song et al, 2020).…”