Atherosclerotic Plaque Rupture

Abstract

The idiom “the straw that breaks the camel’s back” describes scenarios where seemingly minor incidents eventuate in a sudden, unexpected, and often detrimental downfall. In the case of atherosclerosis, over time multiple subclinical cellular events result in the development of unstable, vulnerable atherosclerotic lesions, which leads to the rupture of atherosclerotic plaques, culminating in the often catastrophic clinical manifestation of myocardial infarction or ischemic stroke. In this review, we first summarize lessons learned from autopsy studies, clinical investigations, and animal models mainly published in ATVB . We then present recent experimental studies published in ATVB that shed light on the underlying pathophysiological development of plaque instability and disruption, and how differential and sometimes maladaptive responses at cellular levels contribute to this complex process. These many publications in ATVB are a testament to the journal’s leading role in research on atherosclerotic plaque instability, an area of research with utmost translational relevance. Our understanding of the pathology of unstable, vulnerable atherosclerotic plaques is mainly based on a limited number of postmortem examinations of human coronary arteries and the analysis of resected surgical specimens from patients who underwent carotid endarterectomy and performed for primary/secondary prevention of transient ischemia attack or stroke.1–3 The histopathologic definition of unstable plaques includes, as the most central features, thin fibrous caps (thickness 40% of the total lesion volume).4–7 Importantly, repeated subclinical plaque ruptures, histologically and potentially macroscopically visible as intraplaque hemorrhage, are described as an additional cause of plaque instability.8 From an autopsy series of 800 cases of sudden coronary …