Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study

Abstract

Objective Smooth muscle cells, macrophage infiltration and accumulation of lipids, proteoglycans, collagen matrix and calcification play a central role in atherosclerosis. The early histologic changes of plaque progression from pathologic intimal thickenings (PIT) to late fibroatheroma lesions have not been fully characterized. Methods A total of 151 atherosclerotic coronary lesions were collected from 67 sudden death victims. Atherosclerotic plaques were classified as PIT without macrophage infiltration, PIT with macrophages, and early and late fibroatheromas. Presence of macrophages and proteoglycans (versican, decorin and biglycan) were recognized by specific antibodies while hyaluronan was detected by affinity histochemistry. Lipid deposition was identified by oil-red-O, and calcification was assessed following von Kossa and alizarin red staining. Results Lesion progression from PIT to late fibroatheroma was associated with increase in macrophage accumulation (p<0.001) and decreasing apoptotic body clearance by macrophages (ratio of engulfed-to-total apoptotic bodies) (p<0.001). Lipid deposition in lipid pool of PIT had a microvesicular appearance whereas those in the necrotic core were globular in nature. Overall, the accumulation of hyaluronan (p<0.001), and proteoglycan versican (p<0.001) and biglycan (p=0.013) declined along with lesion progression from PIT to fibroatheromas. Microcalcification was first observed only within areas of lipid pools and its presence and size increased in lesions with necrotic core. Conclusions PIT to fibroatheroma lesions are accompanied by early lipid accumulation, followed by macrophage infiltration with defective clearance of apoptotic bodies along with decrease in proteoglycan and hyaluronan in lipid pools that convert to necrotic cores. Calcification starts in PIT and increases with plaque progression.

Systematic Evaluation of the Cellular Innate Immune Response During the Process of Human Atherosclerosis

“…On the contrary, transition to pathological intimal thickening, the earliest form of progressive atherosclerosis, is characterized by accumulation of ApoB100 within the medial wall, which, in fact, is much earlier than previously reported 29. Demonstration that the transition to irreversible atherosclerosis is associated with a loss of internal elastic lamina integrity hallmarks the beginning of medial and adventitial involvement in atherosclerosis, a phenomenon that warrants further investigation 30, 31…”

Neoatherosclerosis From a Pathologist’s Point of View

“…10,14 Although the precise mechanism of how pathological intimal thickening converts to a fibroatheroma is less clear, the infiltration of macrophages into existing proteoglycan-rich lipid pools is believed to be the defining feature. 16,17 Immune responses along with lipid deposition have also been implicated both in the initiation and propagation of atherosclerotic plaque that results in the chronic inflammation of the vessel wall. 18 Fibroatheromas, characterized by a thick fibrous cap overlying a necrotic core, can be divided into 2 different stages recognized as early or late, based on the discrete collection of cellular debris within the necrotic core, increased cholesterol crystals, and complete degradation of extracellular matrix observed only in late stages.…”

Gestational hypoxia and programming of disease

“…In particular, hypertension is associated with thickening of the walls of both small and large arteries, known as arteriosclerosis (Otsuka et al, 2015). This loss of arterial compliance can lead to altered vessel wall properties and an exaggerated response to vasoconstrictors, both of which increase peripheral vascular resistance.…”

“…Presence of atherosclerotic plaques reduce elasticity of the arterial walls, leading to increased vascular stiffness and widened pulse pressure, both of which are significant risk factors for CVD. Over time, increased plaque size can disrupt blood flow through the vasculature, the consequences of which are specific to the site of the lesion (Otsuka et al, 2015;Wang & Bennett, 2012). Atherosclerosis of the coronary arteries, for example, leads to coronary artery disease whereby the individual experiences reduced cardiac blood flow and susceptibility to heart attack (Otsuka et al, 2015).…”

“…Over time, increased plaque size can disrupt blood flow through the vasculature, the consequences of which are specific to the site of the lesion (Otsuka et al, 2015;Wang & Bennett, 2012). Atherosclerosis of the coronary arteries, for example, leads to coronary artery disease whereby the individual experiences reduced cardiac blood flow and susceptibility to heart attack (Otsuka et al, 2015). Plaques in arteries that direct blood away from the heart and brain can cause peripheral vascular disease, which increases risk of infection, tissue ischaemia and ultimately limb loss if left untreated.…”