Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice.
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.
Napoli
Claudio
C
*Department of General Pathology, Division of Clinical Pathology, Excellence Research Center on Cardiovascular Diseases, and claunap@tin.it lignarro@mednet.ucla.edu.|Whitaker Cardiovascular Institute, Boston University, Boston, MA 02118.|Research Center on Craniofacial Malformations-MRI, School of Medicine, Second University of Naples, Naples 80138, Italy.
Williams-Ignarro
Sharon
S
Division of Anesthesiology and.
de Nigris
Filomena
F
*Department of General Pathology, Division of Clinical Pathology, Excellence Research Center on Cardiovascular Diseases, and.
Lerman
Lilach O
LO
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55905.
D'Armiento
Francesco P
FP
**Department of Biomorphological Sciences, University of Naples Federico II, Naples 80131, Italy.
Crimi
Ettore
E
Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA 01201; and.
Byrns
Russell E
RE
Department of Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1735.
Casamassimi
Amelia
A
*Department of General Pathology, Division of Clinical Pathology, Excellence Research Center on Cardiovascular Diseases, and.
Lanza
Alessandro
A
Research Center on Craniofacial Malformations-MRI, School of Medicine, Second University of Naples, Naples 80138, Italy.
Gombos
Fernando
F
Research Center on Craniofacial Malformations-MRI, School of Medicine, Second University of Naples, Naples 80138, Italy.
Sica
Vincenzo
V
*Department of General Pathology, Division of Clinical Pathology, Excellence Research Center on Cardiovascular Diseases, and.
Ignarro
Louis J
LJ
Department of Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1735 claunap@tin.it lignarro@mednet.ucla.edu.
D000818:Animals; D001161:Arteriosclerosis / Q000151:congenital / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D019587:Dietary Supplements; D018450:Disease Progression; D016166:Free Radical Scavengers / Q000378:metabolism; D006937:Hypercholesterolemia / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D018810:Magnetic Resonance Angiography; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D015996:Survival Rate
D016166:Free Radical Scavengers; D052250:Nitric Oxide Synthase Type III