MEDIAL ELASTIC STRUCTURE ALTERATIONS IN ATHEROSCLEROTIC ARTERIES IN MINIPIGS - PLAQUE PROXIMITY AND ARTERIAL SITE-SPECIFICITY

Using a model of atherosclerosis in minipigs, we analyzed changes in e lastic structure within the medial sections of the abdominal aorta and left interventricular coronary artery both in the vicinity of and dis tal to atheromatous plaques. Twenty-four animals, divided into three g roups, were fed either a control diet or a hypercholesterolemic and hy perhomocysteinic atherogenic diet, alone or in association with an ant ihypertensor, namely isosorbide dinitrate (Risordan(R)). The atherogen ic diet, administered for a period of four months, induced in the mini pig advanced noncalcified atherosclerotic lesions that were histologic ally similar to those found in humans. A morphodensitometric analysis of the medial elastic structures was carried out on images obtained fr om specifically stained transverse arterial sections examined under a light microscope. The volume density of the elastic structures was dim inished in the arterial media of the atherosclerotic animals due to op ening and widening of the fenestrae in the elastic laminae and increas ed communication between the interlamellar spaces. Whereas this elasto lytic process was uniform and independent of the proximity of atheroma tous plaques in the left interventricular coronary artery, it was inte nsified in the vicinity of the plaques in the abdominal aorta. Overall elastolytic activity was increased in the walls of atheromatous arter y in both arterial sites, and metalloproteinases were implied in this increase of activity. We previously reported that treatment with isoso rbide dinitrate significantly reduced the moderate systolic hypertensi on and the increase in transparietal stress observed in the abdominal aorta of atheromatous animals. We report here that isosorbide dinitrat e prevented the atherogenic-diet-induced deterioration of the elastic structure in these arteries; complete inhibition of changes to the ela stic laminae was evident in areas remote from plaque formation, but on ly partial inhibition in the vicinity of such plaques. It did not, how ever, prevent structural damage in the left interventricular coronary artery or modify the increase in parietal elastolytic activity in eith er of the two arteries. This suggests that damage to the elastic struc ture in atheromatous arteries is dependent not only on overall elastol ytic activity but also on localized factors, possibly related to parie tal stresses, affected by the presence of atheromatous plaques.