Experimental hypercholesterolemia induces ultrastructural changes in the internal elastic lamina of porcine coronary arteries

The internal elastic lamina (IEL) serves as a barrier for cells and macromolecules migration between the intima and the media in the vascular wall. Several investigators have reported internal elastic lamina ultrastructural changes in elastic arteries with atherosclerosis. However, no quantitative and qualitative assessment of the internal elastic lamina architecture in muscular arteries such as the coronary circulation during early atherosclerosis have been performed yet. In this study, we therefore evaluated the ultrastructural morphological changes of the IEL in the coronary circulation of pigs fed with high cholesterol diet. Animals were sacrificed after being fed either a high cholesterol diet for 10-12 weeks (n = 5, 12 coronary segments) or a control diet (n = 4, 15 coronary segments). Coronary arteries were analyzed by transmission and scanning electron microscopy. In addition, computerized digital analysis of the images obtained by confocal scanning microscopy was performed for the quantitation of the morphologic changes in the internal elastic lamina. Confocal microscopy and scanning electron microscopy revealed an altered pattern characterized by large oval fenestration formation in the internal elastic lamina of hypercholesterolemic animals. Computerized morphometric analysis of confocal microscopy images demonstrated that compared to controls, the IEL of cholesterol-fed animals was characterized by an increase in the minor diameter of the fenestrae (2.16 +/- 0.04 microm versus 3.32 +/- 0.06 microm, P = 0.003) and a decrease in the fenestrae density (22333 +/- 1334/mm2 versus 17552 +/- 931/mm2, P = 0.015) of the internal elastic lamina. The percentage of the IEL area covered by the fenestrae correlated with the intimal thickness (r = 0.79, P = 0.004). This study demonstrates that experimental hypercholesterolemia is characterized by ultrastructural changes of the internal elastic lamina in the coronary circulation. This study suggests that the IEL may play an important role in the development of structural changes which characterize the early phase of coronary atherosclerosis.