Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state.


Greens needed to activate NRF2 proteins (transcription factors), which prevents plaque adhesion--makes slippery. highest level of blood lutein have healthiest blood vessels with no atherosclerosis; (lutein level mostly a research tool.)

TitleActivation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state.
Publication TypeJournal Article
Year of Publication2009
AuthorsZakkar M, Van der Heiden K, Luong LA, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, Evans PC
JournalArteriosclerosis, thrombosis, and vascular biology
Date Published2009 Nov
KeywordsAnimals, Arteries, Arteritis, Cells, Cultured, Disease Models, Animal, Endothelial Cells, Enzyme Activation, Inflammation Mediators, Male, Mice, Mice, Inbred C57BL, NF-E2-Related Factor 2, p38 Mitogen-Activated Protein Kinases, Phosphorylation, Random Allocation, Sensitivity and Specificity, Shear Strength, Signal Transduction, Thiocyanates

OBJECTIVE: Proinflammatory mediators influence atherosclerosis by inducing adhesion molecules (eg, VCAM-1) on endothelial cells (ECs) via signaling intermediaries including p38 MAP kinase. Regions of arteries exposed to high shear stress are protected from inflammation and atherosclerosis, whereas low-shear regions are susceptible. Here we investigated whether the transcription factor Nrf2 regulates EC activation in arteries.

METHODS AND RESULTS: En face staining revealed that Nrf2 was activated in ECs at an atheroprotected region of the murine aorta where it negatively regulated p38-VCAM-1 signaling, but was expressed in an inactive form in ECs at an atherosusceptible site. Treatment with sulforaphane, a dietary antioxidant, activated Nrf2 and suppressed p38-VCAM-1 signaling at the susceptible site in wild-type but not Nrf2(-/-) animals, indicating that it suppresses EC activation via Nrf2. Studies of cultured ECs revealed that Nrf2 inactivates p38 by suppressing an upstream activator MKK3/6 and by enhancing the activity of the negative regulator MKP-1.

CONCLUSIONS: Nrf2 prevents ECs at the atheroprotected site from exhibiting a proinflammatory state via the suppression of p38-VCAM-1 signaling. Pharmacological activation of Nrf2 reduces EC activation at atherosusceptible sites and may provide a novel therapeutic strategy to prevent or reduce atherosclerosis.

Alternate JournalArterioscler. Thromb. Vasc. Biol.
PubMed ID19729611
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