Pathology of Carotid Artery Restenosis

Descriptive Pathology

Although several animal model systems have been used to study mechanically induced arterial intimal thickening, the dynamic, human in vivo mechanisms leading to recurrent stenosis remain incompletely understood.

In general, some degree of acute mural thrombus formation and acute inflammation can be seen after CEA. Within the first few weeks to months of the arterial manipulation, the restenotic lesion is described as intimal tissue composed of numerous smooth muscle cells, much proteoglycan-rich and collagen-rich extracellular matrix, and a few monocyte/macrophages, and possibly other inflammatory cells. This early-stage lesion thus resembles the diffuse intimal thickening seen in many adult arteries and is best mimicked by animal models of angioplasty-induced arterial injury.

After several months to years, the lesion is generally richer in monocyte/macrophages and might contain a necrotic core, with occasional features of thrombosis and hemorrhage. This later lesion thus better resembles the atherosclerotic plaque, which was the type of lesion originally treated. However, there is much variation in the reported histology, and no definite transition time from the former to the latter is evident. Features of both can also coexist in the same primary or restenotic lesion. For example, although some descriptions of regions of restenotic tissue have focused on features such as stellate smooth muscle cells, a proteoglycan-rich matrix, and occasional organizing thrombi, it is important to remember that all of these features can be seen in primary atherosclerotic lesions that have never undergone interventional procedures. Intimal neovascularization can also be seen in both types of lesions.

Features of carotid lesions that produce symptoms are also not fully clarified. With the primary atherosclerotic plaque, several studies have suggested that in addition to the degree of stenosis, the presence of plaque complications such as ulceration and thrombus formation are important for producing ipsilateral symptoms. Based on correlations between B-mode ultrasound imaging and pathology, many such complicated lesions are described as heterogeneous on ultrasound imaging, whereas many of the early restenotic lesions are described as both asymptomatic and having a homogeneous ultrasound appearance. This homogeneous character is often correlated with diffuse intimal thickening, which is generally devoid of plaque ulcerations or thrombus formation. One is tempted to speculate therefore that the absence of plaque ulcerations and thrombus formation accounts for the lack of symptoms in most carotid restenosis lesions.

Pathogenesis

Based on the author's knowledge of experimental artery wall reactions to injury and results from clinical studies employing ultrasound methods, the presumed processes leading to arterial restenosis can be categorized as follows, although this is likely not a complete listing: smooth muscle cell proliferation, extracellular matrix synthesis, thrombus organization, and artery wall remodeling. These processes can occur to varying degrees in the affected arteries.