Abstract 1604: Diabetes Provokes Atherosclerotic Plaque Instability Rather Than Plaque Expansion in ApoE-deficient Mice
Background Diabetes mellitus (DM) has been deemed as a prior myocardial infarction-equivalent disease. However, the detailed lipid disturbances aggravated by DM and whether these disturbances are related to atherosclerotic plaque instability and progression remain poorly understood. We sought to investigate these issues using streptozocin-induced DM model in ApoE-deficient mice.
Methods ApoE-deficient mice (age: 24 –25 weeks) fed on normal chow were given either streptozocin (DM group) or saline (Control group) injection. Three weeks later, plasma and liver were collected for metabolomic study using 1H-NMR spectroscopy, and brachiocephalic arteries were subjected to morphometric analysis.
Results Forty-five percent of mice in the DM group died during the experimental period, in contrast to no death found in the Control group (p=0.04). Blood glucose, cholesterol and free fatty acid levels were all significantly higher in the DM group (327 ±101 vs. 140±41 mg/dl; 2531±399 vs. 624±96 mg/dl; 3.6±1.4 vs. 1.5±0.1 mM, respectively, all p<0.01). Metabolomic analysis demonstrated that hepatic steatosis was more cholesterol-dominant in the DM group, as compared with that in the Control group. Hepatic and plasma fatty acyl moieties were more saturated in the DM group, with a significant reduction of linoleic acid levels, indicating a more atherogenic lipid profile. In the morphological analysis, although plaque and lumen areas (indexed to vessel size) did not significantly differ between two groups, the lipid core/plaque ratios were significantly higher in the DM group (25±16 vs. 13±12%, p<0.01), with a significant increase of macrophage content (15±11 vs. 8.8±5.5%, p=0.02), indicating a more vulnerable profile of plaques. Consistent with this, buried fibrous layers, which represent the number of previous plaque rupture, were significantly more in the DM group (1.1±0.6 vs. 0.6±0.7 buried layers/plaque, p=0.03).
Conclusion DM results in plaque instability rather than plaque expansion in ApoE-deficient mice. DM related exacerbation of lipid metabolic disturbances may contribute to this high-risk profile.