Accumulation of co-localised unesterified cholesterol and neutral lipids within vacuolised elastin fibres in athero-prone areas of the human aorta

To investigate whether there are alterations of elastin fibres in the arter ial intima at the pre-atherosclerotic stage, grossly normal areas of human thoracic aorta were taken soon after death from 13 healthy trauma victims w hose ages ranged from 16 to 40 years. Two areas were compared: atherosclero sis-prone (AP) areas localised to the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) area s from the ventral aorta. Electron microscopic analysis combined with cytoc hemical staining was applied. Unesterified cholesterol was identified using the filipin-staining technique while neutral lipids were visualised by the OTO-technique. Intimal features were studied by combining the filipin-stai ning and the OTO-technique. Electron microscopical examination showed that in both AR and AP areas, some elastin fibres in the intima were vacuolised. Unesterified cholesterol was found to be predominantly localised in the mu sculoelastic layer, in particular, inside the vacuolised elastin fibres. Th is localisation was seen in all 13 AP areas studied in contrast to the AR a reas where it was observed in only four of 13 aortas studied (P < 0.0005, c hi(2)-test). accumulation of neutral lipids inside vacuolised elastin fibre s was found in five out of 13 AP areas but was not observed in any of the A R areas (P = 0.01, chi(2)). A combination of the filipin-staining and OTO-t echniques showed that some deposits of neutral lipids and unesterified chol esterol within vacuolised elastin fibres were independently located from ea ch other, but more frequently, neutral lipids were co-located with unesteri fied cholesterol. The present observations indicate a difference between AP and AR intimal areas which, in particular, relates to the structure of ela stin fibres in the musculoelastic layer. The observations suggest that alte rations of the extracellular matrix are involved in the trapping and retent ion of cholesterol and neutral lipids within the intima at an early stage i n the development of atherosclerotic lesions. (C) 1999 Elsevier Science Ire land Ltd. All rights reserved.