News Release

Enigmatic role for NF-kappaB in the hardening of arteries

Peer-Reviewed Publication

JCI Journals

A report in the October 15 issue of the Journal of Clinical Investigation resulting from a collaboration led by Menno P.J. de Winther and researchers at Vrije University, Maastricht University, Technical University of Munich, and Harvard Medical School, reveals that inhibition of the transcription factor NF-kappaB increases atherosclerosis – a chronic inflammatory disease that causes the progressive narrowing and hardening of arteries over time.

An initiating event in the development of atherosclerosis is the accumulation within vessels of lipids such as low-density lipoprotein (LDL), which acts as a carrier for cholesterol and fats in the bloodstream. Modification of these lipids induces inflammatory processes, which recruit macrophages from the blood that consume LDL, thereby creating lesions that ultimately cause vessel narrowing and restriction of blood flow.

The role of NF-kappaB in atherosclerosis has been controversial. NF-kappaB is known to induce expression of inflammatory genes that play detrimental roles in atherosclerosis. On the other hand, NF-kappaB is also a survival factor and may promote expression of certain anti-inflammatory agents.

To investigate the role of NF-kappaB activation in macrophages during atherogenesis, de Winter and colleagues studied mice deficient in the LDL receptor and the enzyme IkappB kinase 2, which is essential for NF-kappaB activation. The authors showed that NF-kappaB–defective macrophages enhance, rather than inhibit, atherosclerosis. Lesions were larger in size, more advanced, and contained more necrosis, and early lesions contained more macrophages.

The authors suggest that inhibition of the NF-kappaB pathway may increase the severity of atherosclerosis by affecting the delicate balance between the expression of pro- and anti-inflammatory factors.

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TITLE: Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor–deficient mice

AUTHOR CONTACT:
Menno P. J. de Winther
Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
Phone: +31-43-3881897
Fax: +31-43-3884574
E-mail: dewinther@gen.unimaas.nl

View the PDF of this article at: http://www.jci.org/cgi/content/full/112/8/1176


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