Abstract 460: A Low Carbohydrate Diet Increases Atherogenesis and Decreases Endothelial Progenitor Cells in ApoE−/− Mice
Background: Bone marrow endothelial progenitor cells (EPCs) may play a role in homeostatic maintenance of the endothelium, thereby mitigating atherogenesis. Short-term clinical trials of low carbohydrate diets for weight loss have not demonstrated adverse effects of these diets on serum lipids or C-reactive protein. We examined the effects of these diets directly on atherosclerosis and EPCs.
Methods: Fifty-two ApoE−/− mice were assigned after weaning to a standard chow diet (15% fat, 65% carbohydrate, 20% protein), atherogenic ‘Western’ diet (42% fat, 43% carbohydrate, 15% protein), or a low carbohydrate (‘low-carb’; 43% fat, 12% carbohydrate, 45% protein) diet. After 6 and 12 weeks on the diets, serum lipids, glucose, insulin and interleukin-6 levels were measured. Quantitation of atherosclerotic burden was performed via aortic en face area and aortic sinus plaque volume analyses. Aortic plaque was analyzed for inflammatory cellular infiltrates. Blood and bone marrow were harvested for FACS and quantitation of EPC colony forming units (CFU). Femoral artery ligation was performed to assess neovascularization in mice on these diets as a measure of EPC function.
Results: By 12 weeks of diet, mice on the low-carb diet had more atherosclerosis compared to Western-fed mice, as assessed by aortic en face area (15.2% vs 8.8%; p<0.05) and aortic root plaque area (170 vs 87 x 103 um2; p=0.03) Serum lipids, glucose, insulin and interleukin-6 levels were similar in Western- and low-carb-fed mice. There was no difference in the extent of inflammatory cell infiltration of plaque between Western and low-carb diets. However, by 6 weeks on diet, bone marrow EPCs were decreased by ~45% in the low-carb fed mice compared to both chow- and Western-fed mice (p<0.05 in both cases). Neovascularization after femoral artery ligation was also decreased in wildtype mice fed the low-carb diet compared to those on Western diet (0.45 vs 0.74% recovery; p=0.013).
Conclusions: Atherosclerosis in ApoE−/− mice is increased by a low carbohydrate/high protein diet compared to a Western diet, despite comparable serum lipids, glucose, inflammatory markers and infiltrates. Reductions in EPC number/function suggest decreased vascular regenerative capacity may contribute to these effects.