Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 27; pp. 10479 - 10484
• Main Authors: Napoli, C, Williams-Ignarro, S, de Nigris, F, Lerman, L.O, D'Armiento, F.P, Crimi, E, Byrns, R.E, Casamassimi, A, Lanza, A, Gombos, F
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.07.2006; National Acad Sciences
• Subjects: Animals; Antibodies; Antioxidants; arginine; Arteriosclerosis - congenital; Arteriosclerosis - etiology; Arteriosclerosis - pathology; Arteriosclerosis - prevention & control; ascorbic acid; Atherosclerosis; Atherosclerotic plaque; Biological Sciences; Blood plasma; Dietary Supplements; Disease Progression; Free Radical Scavengers - metabolism; hypercholesterolemia; Hypercholesterolemia - complications; Hypercholesterolemia - enzymology; Hypercholesterolemia - pathology; Lesions; Magnetic Resonance Angiography; Medical treatment; Metabolism; Mice; mortality; Nitric Oxide Synthase Type III - metabolism; Oxidative stress; pathogenesis; physical activity; Physical Conditioning, Animal - physiology; Physical fitness; Rodents; Survival Rate; Thrombosis; Traumatic ruptures; Vascular diseases; vitamin E; vitamin supplements
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0602774103

Moderate physical exercise (PE) combined with metabolic treatment (MT) (antioxidants and L-arginine) are well known to reduce atherosclerotic lesion formation in hypercholesterolemic mice. However, the long-term beneficial effects on unstable atheroma remain poorly understood. We started early PE training in large groups of 6-week-old hypercholesterolemic mice (by graduated swimming) alone or in combination with nutritional supplementation (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% L-arginine added to the drinking water). Inactive controls did not receive PE. The spontaneous development of atherosclerotic plaque rupture (associated with advanced atherosclerosis) and survival rates were evaluated. Moderate PE elicited an increase in plasma levels of nitric oxide. Early combined treatment with PE and MT in the hypercholesterolemic mice significantly reduced lesions (also detected noninvasively at 10 months) and spontaneous atherosclerotic plaque rupture and prolonged survival more effectively than each intervention alone. Thus, early concerted actions of MT and PE improve the natural history of atherosclerotic lesions and reduce the plaque instability in hypercholesterolemic mice.