Abstract-It is generally established that the unstable plaque is the major cause of acute clinical sequelae of atherosclerosis.Unfortunately, terms indicating lesions prone to plaque instability, such as "vulnerable plaque," and the different phenotypes of unstable plaques, such as plaque rupture, plaque fissuring, intraplaque hemorrhage, and erosion, are often used interchangeably. Moreover, the different phenotypes of the unstable plaque are mostly referred to as plaque rupture.In the first part of this review, we will focus on the definition of true plaque rupture and the definitions of other phenotypes of plaque instability, especially on intraplaque hemorrhage, and discuss the phenotypes of available animal models of plaque instability. The second part of this review will address the pathogenesis of plaque rupture from a local and a systemic perspective. Plaque rupture is thought to occur because of changes in the plaque itself or systemic changes in the patient. Interestingly, contributing factors seem to overlap to a great extent and might even be interrelated. Finally, we will propose an integrative view on the pathogenesis of plaque rupture.
Definition of Plaque RuptureIn 1995, the American Heart Association (AHA) Committee on Vascular Lesions developed a numerical classification of the composition and structure of human atherosclerotic lesions. In this classification, "complicated lesions" (type VI lesions), responsible for most of the morbidity and mortality from atherosclerosis, were defined as atheromata (type IV lesions) or fibroatheromata (type V lesions), containing 1 or more surface defects and/or hematoma-hemorrhage and/or thrombus. 1 In 2000, the classification was updated by Stary 2 and modified by Virmani et al. 3 They introduced a more detailed description of atherothrombotic plaques. In contrast to the AHA classification of 1995, the definition of "plaque rupture" is stricter, and the possibilities for atherothrombotic events are extended. Atherothrombotic events are clearly separated into plaque rupture, erosion, and eruptive calcified nodules. Moreover, intraplaque hemorrhages are described as phenomena in lesions that are not necessarily associated with plaque rupture (Figure 1).Because terms like "plaque instability," "plaque vulnerability," "plaque rupture," and "intraplaque hemorrhage" are often used interchangeably, one explanation for the apparent confusion in the literature is the use of a different definition of atherosclerotic plaque rupture. In this review, the stricter definitions of plaque rupture and intraplaque hemorrhage as proposed by Virmani et al 3 are used. Plaque rupture is defined as "an area of fibrous cap disruption whereby the overlying thrombus is in continuity with the lipid core". 3 Intraplaque hemorrhage is defined as the deposition of blood products inside the plaque and is not necessarily associated with atherosclerotic plaque rupture. 2 Because the pathogenesis of plaque erosion and calcified nodules is hardly known, these are excluded from this review.
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