The formation of calcified deposits in intimal thickenings of human ao
rta was studied by electron microscopy. Microzones of calcification we
re detected in about 20% of fatty streaks studied and were located pre
dominantly in the deep musculoelastic layer of the intima, Calcified d
eposits formed only on previously existing structures including extrac
ellular vesicles and unesterified cholesterol. Calcified deposits in t
he musculoelastic layer of the intima localised inside altered elastin
fibres, but initiating the calcification of elastin required the prio
r accumulation of cholesterol esters inside elastin fibres. Go-localiz
ation of calcified deposits and elastin fibres was followed by destruc
tion of elastin. The present study suggests that at an early stage in
the development of atherosclerotic lesions, calcified deposits are for
med by a physicochemical process which is not strongly controlled by t
he intimal cells. The recognition of calcified deposits in intimal thi
ckenings supports the hypothesis that a subset of fatty streaks might
progress to fibrous plaques in human atherosclerosis.