Does Therapeutic Intervention Achieve Slowing of Progression or Bona Fide Regression of Atherosclerotic Lesions?

Abstract

Abstract-This review focuses on the regression of atherosclerosis in humans and experimental animals. It highlights the difficulties to determine unequivocally whether with a given therapeutic intervention, such as diet, drugs, or apheresis, the progression of lesions was curtailed or bona fide regression of atherosclerotic lesions was achieved. It seems appropriate to mention that 2 very different ways to measure regression were used in experimental animals and in humans. Regression in animals was determined mainly in the aorta or coronary arteries isolated at post mortem, and the criteria used were degree of sudanophilia and/or aortic wall thickness and cellular composition or cholesterol content. In humans, the evaluation of regression relied mainly on quantitative coronary angiography. The literature of the past decade is reviewed selectively but not exhaustively, and in some instances, a brief historical overview is given.

Effect of Low Dose Atorvastatin Versus Diet-Induced Cholesterol Lowering on Atherosclerotic Lesion Progression and Inflammation in Apolipoprotein E*3–Leiden Transgenic Mice

“…18 However, our study demonstrates that a 19% reduction of plasma cholesterol by a statin (ie, a cholesterol reduction achieved with most statins at their lowest pill dosage in humans) 19 is already sufficient to reduce lesion progression in apoE*3-Leiden mice. This is in line with observations made in humans in which a comparable reduction (23%) by simvastatin reduced vessel wall thickness and vessel wall area.…”

Elevating High-Density Lipoprotein Cholesterol in Apolipoprotein E-Deficient Mice Remodels Advanced Atherosclerotic Lesions by Decreasing Macrophage and Increasing Smooth Muscle Cell Content

“…These findings were not necessarily expected, given the prevailing view that only limited changes can be induced in lesions after they advance beyond the early stages. 8 Compared with the EKO recipients, the smaller lesion size in the hAI/EKO recipients was attributable, at least in part, to decreased macrophage content. Many benefits of HDL appear to involve monocytes/macrophages directly or indirectly.…”

“…6 There are no data, however, from human or animal studies showing that a sustained and significant elevation of HDL would have beneficial effects on advanced, preexisting atherosclerotic lesions, an important issue given that by age 35 years, 79% of people have a significant lesion burden (with Ͼ40% having advanced lesions in their coronary arteries), 7 and the recent speculation that such lesions have a limited capacity for improvement. 8 Because of the proven efficacy of HDL to retard lesion formation in EKO mice transgenic for hAI (hAI/EKO), we asked whether the plasma lipoprotein environment in hAI/ EKO mice would also promote beneficial changes in preexisting lesions that had advanced beyond the early foam-cell stage. The experimental approach is based on a novel mouse aortic transplantation model that we recently reported.…”

Maternal Hypercholesterolemia and Treatment During Pregnancy Influence the Long-Term Progression of Atherosclerosis in Offspring of Rabbits

“…27 Results also suggest that interventions in mothers may offer long-term benefits to their offspring, in particular treatment with vitamin E, 28 which is considered safe during pregnancy, or newly developed lipid-lowering drugs.…”