Can atherosclerotic plaques regress? Anatomic and biochemical evidence from nonhuman animal models

For at least 60 years, spotty and poorly documented evidence has suggested that atherosclerotic disease in humans might be reversible. Little direct evidence was available until researchers demonstrated that rather advanced atherosclerotic lesions in experimental animals could show marked improvement after blood-lipid-reducing regimens that were often combined with other measures, such as increased ambient oxygen and estradiol therapy. In fact, this combination was used in this laboratory to produce one of the first effective regression studies in the rabbit model. In more recent studies in this laboratory, abundant evidence has been obtained that the advanced, eccentric, largely intimal lesions produced in the rhesus monkey are substantially reversible, and the much more inflammatory, concentric, and often transmural atheroarteritis induced by the same atherogenic ration in the cynomolgus monkeys is much more resistant to effective and beneficial regression. This unusual reaction appears to be due to the circulating immune complexes that participate in the pathogenesis of atherosclerosis in these cynomolgus monkeys, as well as possibly in a number of humans. The evidence for this phenomenon, as well as the varying effects of the lesions induced with contrasting food fats, is summarized in this presentation. Some of the time-related effects of varying interventions when the lesions are studied at 4-month intervals in rhesus and cynomolgus monkeys are also discussed. Other factors that may influence regression are also considered.