Mechanisms Of Macrophage Scavenger Receptors In The Early Stage Of Atherosclerosis Formation

Objective: To clarify the mechanisms of interaction between macrophage scavenger receptor and lipid metabolism in the early stage of atherosclerosis formation. detailly, (1) The effect of transforming growth factor-β1 (TGF-β1) on THP-1 derived macrophage scavenger receptor (ScR) class A and B (ScR-B, CD36) uptaking oxidized low density lipoprotein (ox-LDL) and acetylated LDL (ac-LDL), meanwhile, the effect of TGF-β1 on ScR-A and CD36 mRNA expressions were anylyzed. (2) The effect of Dilazep (DZ) on ScR-A uptaking ac-LDL was calculated. At same time, the effect of DZ on ScR-A and CD36 mRNA expression was also cheked.Methods:Using macrophages derived monocytes and culture cells, to analyze macrophages uptaking of ac-LDL or ox-LDL, further more using Northern bloting method to check ScR-A and CD36 mRNA expression. Detaily (1) Influence of anti TGF-β1 antibody (Anti TGF-β1 Ab) on uptaking of ac-LDL or ox-LDL was measured respectively. Influence of Anti TGF-β1 Ab on the ScR-A and CD36 mRNA expressions in THP-1 derived macrophages was measured meanwhile, respectively. (2) The effect of DZ on uptaking of ac-LDL by ScR-A and ScR-A mRNA expression was measured (3) The effect of DZ on CD36 mRNA expression was measured. Results: (1) Compared with control group of (binding: 8.23μ?g·g-1±1.24 μg·g-1 protein, Association: 45.69 ?μg·g-1±6.92μg·g-1 protein, and degradation: 112.18 ?μg·g-1±20.15μg·g-1 protein), Anti TGF-β1 Ab increased 125I-ac-LDL binding (48.67 ?μg·g-1±6.52μg·g-1protein), Association (412.30μg·g-1±12.21μg·g-1 protein), and degradation (896.48 ?μg·g-1±32.74μg·g-1protein) significantly (P<0.01); Compared with control group (binding 78.56 ?μg·g-1±2.81μg·g-1protein, Association 123.94 ?μg·g-1±12.11μg·g-1 protein, and degradation: 345.38 ?μg·g-1±27.17μg·g-1 protein), Anti TGF-β1 Ab markedly increased 125I-ac-LDL binding 102.32 ?μg·g-1±3.11μg·g-1 protein), Association (412.94 ?μg·g-1±15.21μg·g-1 protein), and degradation (788.94 ?μg·g-1±31.16 μg·g-1 protein), respectively (P<0.01). The ScR-A and CD36 mRNA expressions of THP-1 derived macrophages were increased after treated by Anti TGF-β1 Ab compare with control group. The ratio of ScR-A mRNA of experimental group to control group was 1.7, the ratio of CD36 mRNA was 1.12. (2) Pretreatment of 50 and 100 mmol·L-1 of Dilazep, significantly decreased Ac-LDL binding and degradation with DZ concentration-dependent manner. The macrophage ScR mRNA expression was attenuated by treatment of DZ. (3) The CD36 mRNA expression was markedly attenuated by pretreatment of 50 and 100 mmol·L-1DZ but CD36 mRNA expression was not influenced by treatment of different concentration of DZ on macrophages differentiated from THP-1 monocytes.Conclusion: (1) TGF-β1 can influence the formation and development of As through inhibiting the expressions of ScR-A and CD36, and this depressive effect may be mainly depend on ScR-A. (2) DZ could inhibit ac-LDL uptake through attenuate macrophage ScR-A expression. DZ have preventive effect on atherosclerosis formation through down-regulation of CD36 expression. But CD36 expression was not influenced by treatment of DZ on macrophages differentiated from THP-1 monocytes. These results suggest that DZ have preventive effect in the early stage of atherosclerosis formation.