Regression of Advanced Atherosclerotic Lesions in Swine

Advances in Experimental Dyslipidemia and Atherosclerosis

“…These observations suggest that regression of atherosclerosis in monkeys depends on the degree of their response to dietary cholesterol; hyporesponders showed evidence for regression, whereas hyperresponders did not (Clarkson et al, 1984). Dietary intervention induced regression of early atherosclerotic lesions, but not of advanced lesions, in the abdominal aorta of swine (Daoud et al, 1981). Similar to above observations, neither phytosterol treatment nor low-fat diets caused regression of advanced atherosclerotic lesions in the aortic roots of apo E-KO mice (Moghadasian et al, 1999a).…”

Eradicating Atherosclerotic Events by Targeting Early Subclinical Disease: It Is Time to Retire the Therapeutic Paradigm of Too Much, Too Late

“…In contrast, the same interventions have been reported to substantially, but only partially, regress more advanced plaques (Figure 1). 15,[57][58][59][60]78 Based on the clinical data to date, the same pattern seems to be magnified in the human disease, which occurs over a much longer timescale. In people, it may be that a 50-year-old plaque in a 60-year-old artery that has been neglected for most of that time can no longer fully heal.…”

“…For example, extensive improvements in the plasma lipoprotein profile quickly allow foam cells to emigrate out of the arterial wall and then promote the initiation of a steady stream of healthy macrophages that enter the arterial wall, phagocytose debris, and leave. 57,58 Processes to the right of the vertical dashed line are characteristic of advanced, end-stage plaques and hence appear to be only partially reversable. For example, after extensive improvements in the plasma lipoprotein profile, cholesterol crystals and areas of necrosis within the arterial wall diminish, but slowly and often incompletely.…”

“…For example, after extensive improvements in the plasma lipoprotein profile, cholesterol crystals and areas of necrosis within the arterial wall diminish, but slowly and often incompletely. 15,[57][58][59][60][61] Without adequate management, the progressing plaque expresses two key enzymes, SMase (sphingomyelinase) and LpL (lipoprotein lipase), that synergistically accelerate further retention and aggregation of apoB-lipoproteins onto arterial PGs (proteoglycans). [62][63][64][65] In an end-stage atheroma, MMPs (matrix metalloproteinases) weaken the fibrous cap, thereby rendering the plaque susceptible to rupture or erosion.…”

“…Processes to the left of the vertical dashed line are characteristic of early atherosclerotic plaques and hence remain entirely or nearly entirely reversable. For example, extensive improvements in the plasma lipoprotein profile quickly allow foam cells to emigrate out of the arterial wall and then promote the initiation of a steady stream of healthy macrophages that enter the arterial wall, phagocytose debris, and leave 57,58. Processes to the right of the vertical dashed line are characteristic of advanced, end-stage plaques and hence appear to be only partially reversable.…”