Department of Anatomy and Cell Biology III, University of Heidelberg, INF 307, 69120 Heidelberg, Germany.
Atherosclerosis. 2010 Jun;210(2):407-13. doi: 10.1016/j.atherosclerosis.2010.01.009. Epub 2010 Jan 22.
Experimental study on plaque progression, regression and composition in atherosclerotic thoracic aorta of hypercholesterolemic rabbits after long-term withdrawal of cholesterol-enriched diet (CED).
Rabbits were fed 2% cholesterol for 6 weeks followed by withdrawal periods for 15, 23, 34, 68, or 78 weeks. Cholesterol, triglyceride, and phospholipids levels in blood and cholesterol concentrations in aorta were quantified. Plaque size and cellularity, phenotype of macrophages and smooth muscle cells were (immuno)histomorphometrically analyzed in segments of the thoracic aorta.
After 6 weeks of CED, blood cholesterol levels were about 80-fold higher, whereas atherosclerosis and cholesterol content in the thoracic aorta were only minimally increased. However, the latter significantly increased within 15 weeks after cholesterol withdrawal, while serum cholesterol level was still 10-fold increased. Thereafter plaque area and cholesterol content remained almost unchanged until the end of the study despite a long-term normalization of serum cholesterol level after withdrawal of CED. Directly after 6 weeks of CED the densities of macrophages and apoptotic cells within plaques were highest, decreasing after cholesterol withdrawal, whereas, vice versa the density of smooth muscle cells (SMCs) significantly increased.
We suggest that atherosclerotic plaques respond to long-term withdrawal of CED by decrease in number and phenotype of macrophages and increase of SMCs without regression of the lesion size. The cellular changes are suggested to considerably contribute to higher plaque stability.
研究高胆固醇血症兔长期停食富含胆固醇饮食（CED）后，胸主动脉粥样硬化斑块的进展、消退和组成变化。
兔子喂食 2%胆固醇 6 周后，停食 15、23、34、68 或 78 周。定量检测血液中胆固醇、甘油三酯和磷脂水平及主动脉胆固醇浓度。采用免疫组织形态计量学方法分析胸主动脉节段斑块大小和细胞密度、巨噬细胞和平滑肌细胞表型。
CED 6 周后，血胆固醇水平升高约 80 倍，而主动脉粥样硬化和胆固醇含量仅轻度增加。然而，胆固醇停食后 15 周内，后者显著增加，而血清胆固醇水平仍升高 10 倍。此后，尽管 CED 停食后血清胆固醇水平长期正常化，但斑块面积和胆固醇含量几乎不变，直至研究结束。CED 6 周后，斑块内巨噬细胞和凋亡细胞的密度最高，胆固醇停食后降低，而平滑肌细胞（SMC）的密度显著增加。
我们认为，动脉粥样硬化斑块对 CED 的长期停食反应为巨噬细胞数量和表型减少，SMC 增加，而病变大小无消退。细胞变化可能对斑块稳定性有较大贡献。
