Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis

Abstract

Plaque rupture, usually of a precursor lesion known as a 'vulnerable plaque' or 'thin-cap fibroatheroma', is the leading cause of thrombosis. Less-frequent aetiologies of coronary thrombosis are erosion, observed with greatest incidence in women aged <50 years, and eruptive calcified nodules, which are occasionally identified in older individuals. Various treatments for patients with coronary artery disease, such as CABG surgery and interventional therapies, have led to accelerated atherosclerosis. These processes occur within months to years, compared with the decades that it generally takes for native disease to develop. Morphological identifiers of accelerated atherosclerosis include macrophage-derived foam cells, intraplaque haemorrhage, and thin fibrous cap. Foam-cell infiltration can be observed within 1 year of a saphenous vein graft implantation, with subsequent necrotic core formation and rupture ensuing after 7 years in over one-third of patients. Neoatherosclerosis occurs early and with greater prevalence in drug-eluting stents than in bare-metal stents and, although rare, complications of late stent thrombosis from rupture are associated with high mortality. Comparison of lesion progression in native atherosclerotic disease, atherosclerosis in saphenous vein grafts, and in-stent neoatherosclerosis provides insight into the pathogenesis of atheroma formation in natural and iatrogenic settings.

Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis

“…2014, 2015; Yahagi et al. 2016). Although the general mechanisms of native atherosclerosis are well established, the cause of accelerated atherosclerosis following vascular interventions is unclear.…”

“…2014, 2015; Yahagi et al. 2016). Neoatherosclerosis is by definition characterized by accumulation of lipid‐laden macrophage foam cells and/or calcification within stented arteries (Otsuka et al.…”

“…2014, 2015; Yahagi et al. 2016). Because of the high prevalence, neoatherosclerosis has been proposed to be a major cause of thrombosis during late stent failure (Park et al.…”

“…2013; Yahagi et al. 2016). The atherosclerotic lesions appear already within 1 year after implantation, and between 2 and 5 years after intervention complex lesions with necrotic cores are seen (Motwani and Topol 1998; Kim et al.…”

CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis

“…While most atherosclerotic plaques are clinically silent, a subset of lesions can trigger thrombotic vascular occlusion, leading to unstable angina, myocardial infarction, stroke, or sudden cardiac death. Two morphologically distinct lesion types can lead to occlusive thrombosis: rupture-prone plaques with necrotic cores and thin fibrous caps (thin-cap fibroatheroma [TCFA]) and fibrous plaques with superficial endothelial erosion (4,5). Given the clinical importance of TCFA, understanding the processes that contribute to the development of the necrotic core is essential.…”