It is all c-RELative: a new perspective for a member of the nuclear factor kappa B family

Atherosclerosis is intimately linked to myocardial infarction and stroke, two leading causes of death.Atherosclerotic lesions form in arterial beds and grow over decades, accumulating fatty deposits, fibrous material, diverse immune cells, and vascular smooth muscle cells.For the most part these lesions remain clinically silent until plaque rupture or endothelial erosion arise, exposing the thrombogenic substrate and leading to acute lumen obstruction.Diverse strategies to slow or even reverse atherogenesis have been successful but have yet to completely eliminate risk associated with the disease 1 , so efforts to better understand how and why plaques grow remain important.A central tenet of atherogenesis is the blood flow-dependent localization of plaques.It is now well accepted that lesions form in areas of low or disturbed blood flow, whereas vascular segments where wall shear stress is high or pulsatile (rather than oscillatory) tend to remain plaque free.This notion has placed endothelial cells (EC) at the forefront in the search for clues that would reveal why plaques build up where they do.It has led to two complementary lines of research aimed at understanding why some regions are devoid of plaques and conversely why others are plaque-prone, based on the local hemodynamics.Considerable advances have been made in both cases, highlighting how cells biomechanical cues are relayed through surface structures, activating signal transduction cascades and producing changes in gene expression that can profoundly alter endothelial structure and function .Prominent among the cascades responsive to changes in flow is the nuclear factor kappa B (NF-B) transcription factor family, which include NF-B1 (p50/p105), NF-B2 (p52/p100), RelA (p65), RelB and c-Rel 2 .Members of the family share sequence similarity over a 300-amino-acid Rel homology domain and form homo-or heterodimer transcription factor complexes that bind a broad array of DNA targets, many of which regulate immune responses, proliferation, and survival.The most widely studied form of