Studies of Regression of Advanced Atherosclerosis in Experimental Animals and Man*

Abstract

In general, the results to date in humans and experimental animals seem to indicate that substantial regression of advanced atherosclerosis is possible. The results also indicate that the advanced atherosclerotic lesions are much more likely to respond favorably if the serum cholesterol concentrations are reduced to the minimum that prevails in animals or people who consume a low-fat low-cholesterol diet. In human subjects and in rhesus monkeys, this value appears to be about 150 mg%. Under these circumstances, much of the lipid disappears from the plaques, and the remaining fibrous tissue and cells appear to condense and undergo remodeling, as they do in fracture or wound healing. Additional effort will be required to ascertain how rapidly and how much of the fiber proteins and calcium can be removed from the advanced plaques and to work out methods that will consistently produce regression of advanced atherosclerotic lesions in human subjects. This goal would appear to be worth working toward. Interruption of progression of atherosclerosis appears to be more easily achieved, and it also would appear to be a worthwhile goal. The diagram that is reproduced as FIGURE 2 presents the multiple methods of intervention in atherosclerosis that are now available to the physician and to the patient. To those of us who look on atherosclerosis as an almost completely preventable disease and one that is largely reversible, the following quotation from the perceptive essay by Lewis Thomas seems to be prophetic and most appropriate. An extremely complex and costly technology for the management of coronary heart disease has evolved, involving specialized ambulances and hospital units, all kinds of electronic gadgetry and whole platoons of new professional personnel to deal with the end results of coronary thrombosis. Almost everything offered today for the treatment of heat disease is at this level of technology, with the transplatned and artificial hearts as ultimate examples. When enough has been learned for us to know what really goes wrong in heart disease, we ought to be in a position to figure out ways to prevent or reverse the process; and when this happens, the current elaborate technology will be set to one side.

CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima

“…Previous studies of atherosclerotic plaque progression and regression have revealed the dynamic nature of atherosclerotic lesions and the important role of macrophage neointimal trapping in lesion growth and macrophage emigration to regional lymph nodes in lesion regression (10,11,(30)(31)(32). The mechanisms involved in macrophage trapping in the inflamed atherosclerotic neointima are incompletely understood yet represent a novel target for potential therapeutic intervention.…”

Cascade Filtration for Familial Hypercholesterolemia

“…The roles of factor VIII and vWF and of circulating immune complexes in the formation and evolution of the atherosclerotic lesions is unclear. However they promote concentric transmural plaques that lead to arterial dilatation and a tendency to thrombosis (8), with platelets, macrophages, granulocytes and lysosomal enzymes as mediators of the vessel damage.…”

Aging and atherosclerosis in human and nonhuman primates

“…As suggested by Masoro (51), "...aging and atherosclerosis may merely share the same time frame, or there may be a causal interaction between them". Although animal studies have shown that intrinsic aging processes may enhance susceptibility to atherosclerosis (40,52), chemical analyses of arteries from specimens indicate that aging changes in extracellular matrix differ from those occurring with development of advanced atheroscierotic lesions (41,50). This suggests that atherosclerosis can be dissociated from the intrinsic aging of the arterial wall (50).…”