Table 1.

Concepts on initiation and/or progression of human atherosclerotic lesion. Denomination: terminology used to describe the beginning of atherosclerotic lesion development. Features: hallmarks and triggers of lesion initiation. Lesion progression due to…: hallmarks and triggers of lesion progression (provided that lesion progression is considered).

Denomination	Features	Lesion Progression Due to …	Ref.
fatty streak, minimal sudanophilic intimal deposit	both intra- and extracellular “globules” of lipid, slight increase in interstitial mucinous material	conversion into fibrous plaques	[2]
type I (initial) lesion	isolated macrophage foam cells	small pools of lipid droplets and dead cell remnants as a source of extracellular lipid in addition to macrophage foam cells (preatheroma)	[3,4]
intimal xanthoma	isolated macrophage foam cells	extracellular lipid accumulation (lipid pools) that are rich in extracellular matrix proteoglycans (pathologic intimal thickening (PIT))	[5,6,7]
grade of lipid deposition 1	fatty streaks with extracellular lipids colocalizing with biglycan and decorin in the outer layer of the intima	n/a	[8]
early lesion	plasma albumin and apolipoprotein B insudation	n/a	[9]
early lesion	interstitial lipid deposits resulting from the encrustation or imbibition of fibrin onto or into the intima	n/a	[10]
gelatinous lesion	balances of intact LDL/“deposited” cholesterol and of fibrinogen/fibrin	loss of steady state concentrations reflecting rates of egress of macromolecules depending on molecular sieving (immobilization of LDL by fibrin)	[11]
n/a	n/a	influx-efflux imbalance in the cell and blood vessel wall	[12]
epicardial coronary atherosclerosis	impairment of lymphatic drainage from the coronary arteries (absence of a potential system for removing protein, fluid and lipids from the arterial wall)	impairment of lymphatic drainage from the coronary arteries (absence of a potential system for removing protein, fluid and lipids from the arterial wall)	[13]
prelesional stage	‘inert’ lipoprotein insudation without monocyte/ macrophage infiltration, lipoprotein modification and complement activation	overload of the cholesterol removal machinery, enzymatic modification of LDL, complement activation, persisting macrophages secreting a variety of molecules accelerating lipoprotein retention, plaque instability, and clotting on rupture	[14,15,16,17,18,19,20,21,22,23,24,25]
early fatty streak	intracellular lipid accumulation in SMCs	degeneration of lipid-containing cells with extravasation of lipid particles into the extracellular space	[26]
early lesion	ionic interaction of positively charged regions of apolipoprotein B with matrix proteins, including proteoglycans, collagen, and fibronectin	n/a	[27]
initial lipid deposition	unesterified cholesterol-rich lipid particles	n/a	[28]
fatty streak	LDL accumulation and oxidation preceding intimal accumulation of monocytes	n/a	[29]
n/a	n/a	cholesterol crystals or clefts in the musculoelastic (deep) layer of the intima or in the tunica media	[30]
fatty streak	accumulation of mononuclear cells	n/a	[31,32]
type I (initial) lesion	alteration in electron density of the matrix of lysosomal bodies as well as the formation of lamellar bodies in lysosomes	substantial structural changes of lysosomes in the ‘normal intima-initial lesion-fatty streak’ sequence	[33,34]
early lesion	unesterified, crystalline cholesterol	n/a	[35,36]
initial lesion	miRNAs mediating cellular regulation in endothelial activation and inflammation, differentiation of macrophages and their polarization, having important functional properties in lipoprotein homeostasis and playing a central role in the mechanisms determining SMC phenotype	miRNAs mediating cellular regulation in endothelial activation and inflammation, differentiation of macrophages and their polarization, having important functional properties in lipoprotein homeostasis and playing a central role in the mechanisms determining SMC phenotype	[37,38,39,40,41]