Calorie restriction prevents the occlusive coronary vascular disease of autoimmune (NZW x BXSB)F1 mice.
Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease (CVD) with myocardial infarction. To determine whether this murine lupus-associated CVD can be prevented by the reduction of dietary calories, male W/BF1 mice were separated into five experimental groups and fed either ad libitum (designated group A, n = 50), fed 32% fewer calories of an otherwise comparable diet (designated group B6, n = 20), or initially fed ad libitum and then switched to reduced calorie intake (RCI) feeding at ages 14, 17, or 22 weeks (designated B14, n = 10; B17, n = 20; or B22, n = 20). Occlusive CVD was prevented by RCI. Life-span was significantly extended among the early onset RCI cohorts, B6 and B14 (P = 0.0001 and P = 0.005), compared to group A mice. Mean anti-cardiolipin autoantibody titers and mean levels of circulating immune complexes were also lowered in RCI mice when all RCI mice were compared to ad libitum fed group A mice. Histological grades of both coronary vascular and glomerular lesions were significantly less than those of group A mice (P < 0.001). Immunoprecipitates indicative of immunoglobulin deposition within coronary or glomerular vascular walls were also substantially less than those of group A mice. These findings indicate a possible causal role for anti-cardiolipin autoantibody in development of autoimmune CVD in W/BF1 mice and suggest that regulating dietary calories can influence the mechanism involved in pathogenesis of autoimmune-associated CVD development.
Mizutani
H
H
Department of Pediatrics, University of South Florida, All Children's Hospital, St. Petersburg 33701.
Engelman
R W
RW
Kinjoh
K
K
Kurata
Y
Y
Ikehara
S
S
Matsuzawa
Y
Y
Good
R A
RA
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000517:prevention & control; D001835:Body Weight; D002308:Cardiolipins / Q000276:immunology; D003331:Coronary Vessels / Q000473:pathology; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D004038:Diet, Reducing; D002149:Energy Intake; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains
D001323:Autoantibodies; D002308:Cardiolipins; D004247:DNA