Reversal of Atherosclerosis: Comparison of Non-Human Primate Models
Numerous reports attest to the usefulness of non-human primates for the study of experimental atherogenesis. During the past decade monkeys have also been utilized for investigations of lesion reversal (Wissler and Vesselinovitch 1977). Dietary regimens designed to reduce serum lipids as well as pharmacological and surgical interventions have been tested in six species. These include one new world species, the squirrel monkey (Saimuri sciureus), and five old world species, i.e., rhesus (Macaca mulatta), cynomolgus (Macaca fascicularis), stumptail (Macaca arctoides), African green monkeys (Cercopithecus aethiops), and baboon (Genus Papio). The approaches used thus far to influence the fate of experimentally induced atherosclerotic lesions are summarized in Table 1 (Armstrong and Megan 1974; Clarkson et al. 1979; De Palma et al. 1977; Hollander et al. 1979; Howard and Patelski 1974; Malinow et al. 1978; Maruffo and Portman 1968; Pick et al. 1978; Stary et al. 1977; Strong et al. 1977; Tucker et al. 1971; Vesselinovitch et al. 1979; Wissler 1979). Each of the primate models has shown special features of lesion configuration and composition during both induction and regression. The rhesus monkey has been the most widely studied (Armstrong and Megan 1974; Clarkson et al. 1979; Stary et al. 1977; Strong et al. 1977; Vesselinovitch et al. 1976; Wissler and Vesselinovitch 1977). Regression of “diet-induced” atherosclerosis in this species is characterized by a decrease in lipids and collagen within lesions as well as resolution of both necrosis and calcification. These regressive or healing changes are associated with a substantial reduction in degree of lumen obstruction. Although the lesions may be reduced readily by any one of several regimens, induction of severe coronary artery atherosclerosis appears to require specially severe atherogenic regimens for extended periods and/or special ancillary models of vessel injury. Lesions induced in the cynomolgus differ from those noted in the rhesus or in humans. In the cynomolgus large numbers of foam cells accumulate in the media and adventitia in association with marked fibroplasia and calcification. Intimal lesions are similar in composition and appear to heal after therapy, but there is little associated reduction of luminal narrowing of affected coronary or peripheral arteries (Hollander et al. 1979; Vesselinovitch and Wissler 1979). In contrast to the rhesus, however, induction of severe coronary artery lesions in the cynomolgus can be achieved in a relatively short time and may result in cardiovascular complications similar to those seen in man. These include coronary stenosis (M Kramsh 1979, personal communication) and development of severe cerebral artery atherosclerosis (Malinow et al. 1978). Lesion regression in the cynomolgus includes decrease of cholesterol content and disappearance of foam cells from the vessel wall. It may be speculated that great preponderance of “foam cells” represents a different cellular pathogenesis which results in a lesion type that is much less responsive to regression by means of serum cholesterol reduction. Despite the dissimilarities from human disease, the cynomolgus model would appear to be useful for the study of matrix protein in lesion regression and for the study of the role of calcium in lesion histogenesis (Armstrong and Megan 1974; Hollander et al. 1979).
KeywordsCholesterol Hydrolysis Corn Foam Agarose
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