Atherosclerotic Plaque Healing

Atherosclerotic plaques typically develop over a period of years or decades. In contrast, the thrombotic complications of atherosclerotic disease occur suddenly, often without warning.1 The notion that acute coronary syndromes develop from the rupture or superficial erosion of an atherosclerotic plaque is an oversimplification of a process involving plaque activity, blood thrombogenicity, and healing.2,3 Pathological studies have shown that many (if not most) atherosclerotic plaques destabilize without resulting in a clinical syndrome.4,5 The occurrence of an acute coronary syndrome probably depends on the disruption of a balance between instability ("activation") and healing ("passivation") of an atherosclerotic plaque. During the past 30 years, research efforts have mostly been focused on the mechanisms of plaque instability.2,3 Yet the risk of acute myocardial infarction or sudden death from coronary causes remains difficult to predict,6 suggesting that other pathogenic mechanisms should also be investigated. Recently, the notion that plaque healing may play a key role in the natural history of atherosclerotic disease has been gaining attention, in part because of the development of new imaging techniques, allowing in vivo study of the morphologic features of atherosclerotic plaque.7,8 This review examines the mechanisms of atherosclerotic plaque healing, their role in the progression of atherosclerotic disease and in the development of acute coronary syndromes, and the clinical and potential therapeutic implications of the healing process.