Translational studies of a20 in atherosclerosis and cardiovascular disease

Cardiovascular disease (CVD) is the biggest killer in the Western World despite significant advances in understanding its molecular underpinnings. Chronic inflammation, the classical hallmark of atherogenesis is thought to play a key pathogenic role in the development of atherosclerotic lesions from initiation of fatty streaks to plaque rupture. Over-representation of mostly pro-inflammatory nuclear factor kappa B (NF-KB) target genes within atherosclerotic lesions has led to the common-held belief that excessive NF-KB activity promotes and aggravates atherogenesis. However, mouse models lacking various proteins involved in NF-KB signaling have oftenresulted in conflicting findings, fueling additional investigations to uncover the molecular involvement ofNF-KB and its target genes in atherogenesis. Tn this chapter we will review the role of the NF-KB-regulated, yet potent NF-KB inhibitory and anti-inflammatory gene A20/TNF AIP3 in atherogenesis, and highlight the potential use of its atheroprotective properties for the prevention and treatment of cardiovascular diseases.