Endothelium and Systemic Inflammation: Role of Nuclear Transcription Factors and Therapeutic Possibilities (Literature Review)

N.I. Degtjar, N.D. Gerasimenko, M.S. Rasin


Endothelium plays a crucial role in human physiology and pathology. Endothelial dysfunction: formation of proinflammatory and prothrombotic phenotype of endothelial cells (EC), excessive production of inflammatory cytokines, reduced production of vasodilators and increased — of vasoconstrictors and prothrombotic mediators is the basis of the pathogenesis of systemic inflammation (SI) and diseases associated with it: hypertension, atherosclerosis, coronary heart disease, obesity, diabetes mellitus 2 type. Nuclear transcription factor kappa B (NFkB) is the main inducer of SI in the endothelial cells, and peroxisome proliferator-activated receptors (PPAR-α, -β/-δ and -γ), NFkB antagonists, are the regulators of SI severity. Studying the molecular mechanisms of NFkB and PPAR action enables the use of NFkB antagonist — metformine, and PPAR-γ agonist — pioglitazone in the treatment of diseases associated with SI, as well as hope for the creation of new drugs.


endothelium; endothelial dysfunction; systemic inflammation; nuclear transcription factor kappa B; peroxisome proliferator-activated receptors; metformin; pioglitazone


Kajdashev IP Activation of NFkB by metabolic syndrome. Physiologic journal.-v. 58.- № 1. - P. 93-101.(in Rus).

RasinMS. Roleofperoxisome proliferator-activated receptors in physiology and pathology of the endothelium. . Krovoobig and hemostasis.2012.-v 4.-PC. 50-56 (in Rus)..

AvogaroA., MattiaAlbiero, LisaMenegazzo, SauladeKreutzenberg, GianPaoloFadini. Endothelial Dysfunction in Diabetes. The role of reparatory mechanisms. Diabetes Care.- 2011.- 34 (Supplement 2).- S285-S290.- doi: 10.2337/dc11-s239

Badrov MB, Freeman SR, Zokvic MA, Millar PJ, McGowan CL.Isometric exercise training lowers resting blood pressure and improves local brachial artery flow-mediated dilation equally in men and women.Eur J Appl Physiol.- 2016.-v.116(7):1289-96. doi: 10.1007/s00421-016-3366-2.

dePunder K., PruimboomL. Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability. Front Immunol.-2015.- 6.-P. 223.-doi: 10.3389/fimmu.2015.00223. eCollection 2015

Hamer M, Sabia S, Batty GD, Shipley MJ, Tabák AG, Singh-Manoux A, Kivimaki M. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation.-.2012.-v.126(8).-P.:928-33. doi: 10.1161/CIRCULATIONAHA.112.103879.

Huang NL, Chiang SH, Hsueh CH, Liang YJ, Chen YJ, Lai LP. Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation. Int J Cardiol. 2009 May 15;134(2):169-75.

QuyyumА.А., Riyaz S. Patel. EndothelialDysfunctionandHypertensionCauseorEffect? Hypertension.2010/-55: 1092-1094.-DOI:10.1161/HYPERTENSIONAHA.109.148957

Kempe S., Kestler H., Lasar F., Wirth T. NF-κB controls the global pro-inflammatory response in endothelial cells: evidence for the regulation of a pro-atherogenic program. NuclearAcidResearch 2015.-33 (16).- 5308-5319.- . doi: 10.1111/j.1463-1326.2010.01349

Laganà AS, Vitale SG, Nigro A, Sofo V, Salmeri FM, Rossetti P, Rapisarda AM, La Vignera S, Condorelli RA, Rizzo G, Buscema M Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives.Int J Mol Sci.- 2016.-v.17(7). pii: E999. doi: 10.3390/ijms1707099

Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab.-2011.-v.13.-P.221–228/ doi: 10.1111/j.1463-1326.2010.01349

Lawrence, Toby. “The Nuclear Factor NF-κB Pathway in Inflammation.” Cold Spring Harbor Perspectives in Biology.- 2009.-v. 79(13 Suppl 1).-:S 58-62.: DOI:10.1212/WNL.0b013e3182695836

Madden J.A. Role of the vascular endothelium and plaque in acute ischemic stroke. Neurology 2012; 79 (13) Supplement 1:S 58-S62. PMID:23008414., DOI: 10.1212/WNL.0b013e3182695836

Plutzky J1. The PPAR-RXR transcriptional complex in the vasculature: energy in the balance. Circ Res.-2011.-v.108(8).-P.:1002-16. doi: 10.1161/CIRCRESAHA.110.226860

Rodríguez-Hernández H, Luis E. Simental-Mendía, Gabriela Rodríguez-Ramírez, and Miguel A. Reyes-Romero. Obesity and Inflammation: Epidemiology, Risk Factors, and Markers of Inflammation. International Journal of Endocrinology. Volume 2013 (2013), Article ID 678159,

Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med.- 2014-;76(3).-:181-9ю doi: 10.1097/PSY.0000000000000049

RuiTian,GonglinHou Dan Li, and Ti-Fei Yuan. A Possible Change Process of Inflammatory Cytokines in the Prolonged Chronic Stress and Its Ultimate Implications for Health. The Scientific World Journal. Volume 2014 (2014) 780616. doi: 10.1155/2014/780616.

SakataniY, MiyoshiT, OeH, NodaY, OhnoY, NakamuraK, SaitoY, OsawaK, MoritaH, KohnoK, ItoH. Pioglitazone prevents the endothelial dysfunction induced by ischemia and reperfusion in healthy subjects. CardiovascPharmacol.-2014.-;64(4).-Р.326-31

Schernthaner G., Craig J. Currie, Gerit-Holger Schernthaner. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabetes Care.-2013.-v.36. Suppl 2.-P. S155-61

ViolletВ., Bruno Guigas, Nieves Sanz Garcia, Leclerc J, Foretz M, AndreelliF..Cellular and molecular mechanisms of metformin: an overview.ClinSci (Lond).-2012.-v. 122(6).-Р. 253–270.

Virdis A. High Blood Press. Cardiovasc Prev. 2016.-23(2).-Р. :83-5. doi: 10.1007/s40292-016-0133-8.

Copyright (c) 2016 HYPERTENSION

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2018


   Seo анализ сайта