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How greens may protect the heart
Sulforapane is found in broccoli and brussel sprouts
Researchers have discovered a possible reason why green vegetables such as broccoli, cabbage and cauliflower are good for the heart.
Their work suggests a chemical found in the vegetables can boost a natural defence mechanism to protect arteries from disease.
The Imperial College London team hope their work could lead to new dietary treatments to prevent heart problems.
Details appear in Arteriosclerosis Thrombosis and Vascular Biology.
Much heart disease is caused by the build up of fatty plaques in the arteries known as atherosclerosis.
However, arteries do not get clogged up with these plaques in a uniform way.
Bends and branches of blood vessels - where blood flow is disrupted and can be sluggish - are much more prone to the build-up.
The latest study has shown that a protein that usually protects against plaque build up called Nrf2 is inactive in areas of arteries that are prone to disease.
However, it also found that treatment with a chemical found in green "brassica" vegetables such as broccoli can activate Nrf2 in these disease-prone regions.
Lead researcher Dr Paul Evans said: "We found that the innermost layer of cells at branches and bends of arteries lack the active form of Nrf2, which may explain why they are prone to inflammation and disease.
"Treatment with the natural compound sulforaphane reduced inflammation at the high-risk areas by 'switching on' Nrf2.
"Sulforaphane is found naturally in broccoli, so our next steps include testing whether simply eating broccoli, or other vegetables in their 'family', has the same protective effect.
"We also need to see if the compound can reduce the progression of disease in affected arteries."
Professor Peter Weissberg, medical director of the British Heart Foundation, which funded the research, said: "These fascinating findings provide a possible mechanism by which eating vegetables protects against heart disease.
"As well as adding evidence to support the importance of eating 'five-a-day', the biochemistry revealed in this research could lead to more targeted dietary or medical approaches to prevent or lessen disease that leads to heart attacks and strokes."
Using normal mice, and mice engineered to lack the Nrf2 protein, the research found that in straight sections of arteries Nrf2 was present in the endothelial 'lining' cells.
Through its action on other proteins, it prevented the cells from becoming inflamed, an early stage in the development of atherosclerosis.
In the lining cells of disease-prone sites - such as bending or branched arteries - Nrf2 was attached to a protein that made it inactive. This stifled its protective properties.
But the addition of sulforaphane re-activated Nrf2 in the disease-prone regions of the artery, restoring the cells' ability to protect themselves from becoming inflamed.
The researchers believe that this will enable these artery regions to remain healthy for longer, or even reduce the progression of existing disease.
Arteriosclerosis, Thrombosis, and Vascular Biology. 2009
Published online before print September 3, 2009, doi: 10.1161/ATVBAHA.109.193375
Submitted on February 16, 2009 Accepted on August 18, 2009
Activation of Nrf2 in Endothelial Cells Protects Arteries From Exhibiting a Proinflammatory State
Mustafa Zakkar ; Kim Van der Heiden ; Le Anh Luong ; Hera Chaudhury ; Simon Cuhlmann ; Shahir S. Hamdulay ; Rob Krams ; Indika Edirisinghe ; Irfan Rahman ; Harald Carlsen ; Dorian O. Haskard ; Justin C. Mason ; and Paul C. Evans *
From the British Heart Foundation Cardiovascular Sciences Unit (M.Z., K.V.d.H., L.A.L., H.C., S.C., S.S.H., D.O.H., J.C.M., P.C.E.), National Heart and Lung Institute, Imperial College London, UK; the Department of Bioengineering (S.C., R.K.), Imperial College London, UK; University of Rochester Medical Center (I.E., I.R.), Rochester, NY; and the Department of Nutrition (H.C.), University of Oslo, Norway.
* To whom correspondence should be addressed. E-mail: firstname.lastname@example.org.
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.
Key words: Nrf2 • arterial endothelium • shear stress • sulforaphane • proinflammatory activation • p38 • MKK3/6 • MKP-1
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