CALORIE RESTRICTION PREVENTS THE OCCLUSIVE CORONARY VASCULAR-DISEASE OF AUTOIMMUNE (NZW X BXSB)F-1 MICE

Male (NZW x BXSB)F-1 (W/BF1) mice develop systemic autoimmunity involv ing autoantibodies, thrombocytopenia, lupus nephritis, and coronary va scular 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 experimenta l groups and fed either ad libitum (designated group A, n = 50), fed 3 2% fewer calories of an otherwise comparable diet (designated group B- 6, n = 20), or initially fed ad libitum and then switched to reduced c alorie intake (RCI) feeding at ages 14, 17, or 22 weeks (designated B- 14, n = 10; B-17, n = 20; or B-22, n = 20). Occlusive CVD was prevente d by RCI. Life-span was significantly extended among the early onset R CI cohorts, B-6 and B-14 (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 RC I mice were compared to ad libitum fed group A mice. Histological grad es of both coronary vascular and glomerular lesions were significantly less than those of group A mice (P < 0.001). Immunoprecipitates indic ative of Immunoglobulin deposition within coronary or glomerular vascu lar walls were also substantially less than those of group A mice. The se findings indicate a possible causal role for anti cardiolipin autoa ntibody in development of autoimmune CVD in W/BF1 mice and suggest tha t regulating dietary calories can influence the mechanism involved in pathogenesis of autoimmune-associated CVD development.