Systems Biology and Noninvasive Imaging of Atherosclerosis

Atherosclerosis is a systemic disease of the arterial vessel wall. Although the mortality due to cardiovascular events is decreasing, the prevalence of atherosclerosis and its comorbidities, and the consequent heath care costs are expected to rise sharply in the near future.1Because the precise cause and pathogenesis of this complex, multifactorial disease are still not fully understood, the clinical assessment of cardiovascular risk has been traditionally based on population risk factors (RFs).2 However, this approach still largely fails to capture the individual’s cardiovascular risk: most cardiovascular events occur in patients with 1 or few traditional RFs, whereas individuals classified as high risk may never experience clinical events.3The past 10 years have seen a significant paradigm shift in our understanding of the mechanisms of atherogenesis. From being considered the mere result of passive lipid accumulation in the vessel wall, atherosclerosis is now classified as an active inflammatory condition.4,5 The presence of abundant, active inflammatory cells is a known hallmark of high risk, vulnerable atherosclerotic plaques.4,5 Many studies have identified several systemic proinflammatory conditions (such as lupus,6 rheumatoid arthritis,7–9 and primary cardiovascular events themselves10) as emerging, independent RFs for atherosclerosis. New evidence suggests that atherosclerosis arises from the complex influence of genetic, environmental, and behavioral variables on systemic and local inflammation through a complex network of molecules, cells, and organs.Thanks to the recent technological advancements of high-throughput ‘-omics’, a plethora of the genes, proteins, and cells involved in the atherosclerotic cascade have already been identified. However, many steps still need to be taken to fully exploit this information, and improve patients’ risk stratification and antiatherosclerotic therapies. The mutual relationship between genetic and molecular key drivers, and their interplay in peripheral blood, atherosclerotic plaques and other organs …