Abstract 1646: Differential Role and Tissue Specificity of Interleukin-1α Gene Expression on Atherogenesis and Lipid Metabolism
Objective: We examined the role of IL-1α in atherogenesis and focused on the contribution of IL-1α and IL-1β expressed by bone marrow-derived cells to atherogenesis.
Methods and Results: The effect of atherogenic diet on atherogenesis in wild type C57Bl/6 was compared to IL-1α or IL-1β deficient mice. IL-1α KO had lower weight gain and higher total cholesterol levels, compared to WT and IL-1β KO mice (398±10; 266±19; 223±13 mg/dl, respectively, p<0.001), due to higher non-HDL cholesterol. Nevertheless, aortic sinus lesion area was 56% lower in IL-1α Κα (6,084±1,253 versus 13,932±2,788 μm2, p<0.05) and 50% lower in IL-1β Κα (6,860±907 μm2, p=0.08), compared to WT mice. Likewise, SAA levels in IL-1α KO mice were markedly lower compared to WT and IL-1β KO mice (31±14; 220±33 and 106±39 μg/ml, respectively, p<0.001). Irradiated C57Bl/6 mice transplanted with either IL-1+/+, IL-1α−/− or IL-1β−/− bone marrow cells, had similar lipoprotein levels. Aortic sinus lesion area was 59% lower in IL-1α −/− transplanted (8,077±1,821 versus 19,545±2,496 μm2, p<0.05) compared to IL-1+/+ transplanted mice. IL-1β deficiency in bone marrow cells did not affect atherogenesis.
Conclusions: We demonstrated that early lesion formation is accelerated specifically by bone marrow-derived IL-1α. Furthermore, we showed that expression of IL-1α in cells other than bone marrow plays a role in non-HDL cholesterol metabolism.