REDUCTION OF SERUM-CHOLESTEROL LEVELS ALTERS LESIONAL COMPOSITION OF ATHEROSCLEROTIC PLAQUES - EFFECT OF PRAVASTATIN SODIUM ON ATHEROSCLEROSIS IN MATURE WHHL RABBITS

We examined whether serum cholesterol reduction alters the lesional co mposition of atherosclerotic plaques. To reduce serum cholesterol leve ls, we gave pravastatin sodium, a 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, to mature Watanabe heritable hyperlipidemic rab bits, an LDL receptor-deficient animal model, for 48 weeks. Atheroscle rotic lesions were immunohistochemically and conventionally stained an d each lesional component area was measured by a color image analyzer. Compared with those of a placebo group, serum LDL cholesterol levels were reduced by 22% (P < .05). Data for atherosclerosis indicated a si gnificant decrease in percent of surface lesion area (26% reduction) a nd in intimal thickening (30% reduction) in the abdominal aorta, as we ll as in coronary stenosis (29% reduction). Data for lesional composit ion indicated a significant decrease in the percent area of macrophage plus extracellular lipid deposits in aortic lesions (32% reduction) a nd coronary lesions (45% reduction). A significant increase was observ ed in the percent area of collagen in aortic lesions and in the percen t area of smooth muscle cells in coronary lesions. The plaques seemed to become stable lesions as a result of pravastatin treatment. In conc lusion, a long-term reduction of serum LDL cholesterol reduced lipid-r elated lesional components, in addition to suppressing the progression of established atherosclerosis.