Food restriction is a promising therapy for many age-associated pathologies as it stimulates the health-supportive mechanism autophagy. Because atherosclerosis is an inflammatory, age-related disease, dietary modification can be an important strategy in preventing atherosclerotic plaque development. A cholesterol-supplemented diet, used to induce plaque formation in rabbits, induces a pronounced hypercholesterolemia, which can be reversed after 4 weeks of normal diet. However, food restriction induces a further increase in circulating LDL cholesterol. These elevated cholesterol levels are associated with the induction of autophagy. Although neither a short-term normal diet nor food restriction alters plaque size, rabbits fed a normal diet show signs of increased plaque stability such as elevated collagen content and decreased expression of vascular cell adhesion molecule (VCAM)-1. Surprisingly, these favorable effects are not present after 4 weeks of food restriction. On the contrary, atherosclerotic plaques of food-restricted rabbits displayed enhanced apoptosis, a process known to further undermine plaque stability. In conclusion, severe short-term food restriction in rabbits prevents stabilization of atherosclerotic plaques as observed after regular cholesterol withdrawal via a normal diet.
Part of the book: Atherosclerosis