Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions.

The clinical manifestations of atherosclerosis are nowadays the main cause of death in industrialized countries, but atherosclerotic disease was found in humans who lived thousands of years ago, before the spread of current risk factors. Atherosclerotic lesions were identified on a 5300-year-old mummy, as well as in Egyptian mummies and other ancient civilizations. For many decades of the twentieth century, atherosclerosis was considered a degenerative disease, mainly determined by a passive lipid storage, while the most recent theory of atherogenesis is based on endothelial dysfunction. The importance of inflammation and immunity in atherosclerosis’s pathophysiology was realized around the turn of the millennium, when in 1999 the famous pathologist Russell Ross published in the New England Journal of Medicine an article entitled “Atherosclerosis – an inflammatory disease”. In the following decades, inflammation has been a topic of intense basic research in atherosclerosis, albeit its importance has ancient scientific roots. In fact, in 1856 Rudolph Virchow was the first proponent of this hypothesis, but evidence of the key role of inflammation in atherogenesis occurred only in 2017. It seemed interesting to retrace the key steps of atherosclerosis in a historical context: from the teachings of the physicians of the Roman Empire to the response-toinjury hypothesis, up to the key role of inflammation and immunity at various stages of disease. Finally, we briefly discussed current knowledge and future trajectories of atherosclerosis research and its therapeutic implications.