Abstract 8167: MiR-424 Promotes the Differentiation of Monocytes to Macrophages in Patients with Coronary Artery Disease, but Can Be Inhibited by Isoflavone In Vitro
MiR-424 has been demonstrated to inhibit the expression of its target protein Nuclear factor I-A (NFI-A) in monocytes and promote the differentiation of monocytes to macrophages in hemopoiesis. This differentiation is also one of the pivotal steps in atherosclerosis. Whether miR-424 has a potential role in the atherosclerosis has been still unknown. Isoflavone has been proved to be an agonist of PPARγ and play anti-atherosclerotic roles by reducing the level of IL-6 and TNF-α in vitro. We assessed the hypothesis that miR-424 might participate the progression of atherosclerosis by inhibiting the expression of NFI-A in monocytes and promoting the differentiation of monocytes to macrophages. Isoflavone might reduce the level of miR-424 in ox-LDL stimulated monocytes to prevent the differentiation of monocytes to macrophages in vitro. Totally 50 subjects were enrolled and divided into three groups: acute myocardial infarction (AMI) group, unstable angina (UA) group and control group. The relative expressions of miR-424 and NFI-A in peripheral monocytes were determined. In vitro, monocytes from healthy subjects were cultured with ox-LDL or ox-LDL combined with isoflavone to clarify whether isoflavone could inhibit the expression of miR-424 in ox-LDL stimulated monocytes. The relative expression levels of miR-424 were significantly increased in UA (1.38±0.33 vs 1.00±0.21, P<0.05) and AMI (3.69±0.92 vs 1.00±0.21, P<0.001) groups as compared to controls. The expression of NFI-A was significantly reduced in UA group, even lower in patients with AMI (AMI: 0.17±0.03; UA: 0.62±0.03; Control: 1.00±0.09). In vitro, the relative level of miR-424 was significantly increased (5.22±0.75 vs 1.02±0.11, P<0.001) in ox-LDL stimulated monocytes but obviously reduced (1.48±0.17 vs 5.22±0.75, P<0.01) after isoflavone added. The levels of IL-6 (10.49±2.15 pg/ml vs 17.92±2.47 pg/ml, P<0.01) and TNF-α (42.81±2.62 pg/ml vs 187.19±7.35 pg/ml, P<0.001) were also significantly reduced in ox-LDL combined isoflavone group as compared to ox-LDL alone group. Conclusively, miR-424 promotes the progression of atherosclerosis by inhibiting the expression of NFI-A in monocytes. Isoflavone can inhibit the increased level of miR-424 in ox-LDL stimulated monocytes in vitro.
- © 2011 by American Heart Association, Inc.