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<p>Elevated blood low-density lipoprotein (LDL) levels are a major risk factor for cardiovascular disease. Increasing LDL receptor (LDLR) expression effectively reduces blood LDL and serves as a key therapeutic strategy for preventing and treating cardiovascular disease. However, it remains unclear how LDLR in different aortic cells contributes to atherosclerosis progression. In this study, we found that hepatocyte-specific deletion of <i>Ldlr</i> in combination with high-fat, high-cholesterol diet feeding induced hypercholesterolemia and atherosclerosis in mice. On this background, further deletion of <i>Ldlr</i> in endothelial cells or smooth muscle cells had no significant effects on atherosclerosis, whereas myeloid-selective ablation of <i>Ldlr</i> markedly attenuated atherosclerotic plaque formation. The decreased percentages of T cells and natural killer T cells in the aorta of mice lacking <i>Ldlr</i> in myeloid cells partially explained the reduced atherosclerotic burden, despite that bone marrow-derived macrophages from <i>Ldlr</i> knockout mice could still be induced to form foam cells <i>in vitro</i>. Therefore, LDLR is better to be elevated in a cell-specific manner for cardiovascular disease prevention and treatment.</p>

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Cell type-specific contribution of low-density lipoprotein receptor to atherosclerosis

  • 期刊论文

  • 发表日期：

    2026年1月15日

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  • Wei-Hui Li,
  • Yu-Liang Zhang,
  • Ya-Fen Zhang,
  • Zhenyang Yu,
  • Liang Chen,
  • Hao-Yu Fang,
  • Liang Cheng,
  • Bao-Liang Song,
  • Jie Luo

摘要

Elevated blood low-density lipoprotein (LDL) levels are a major risk factor for cardiovascular disease. Increasing LDL receptor (LDLR) expression effectively reduces blood LDL and serves as a key therapeutic strategy for preventing and treating cardiovascular disease. However, it remains unclear how LDLR in different aortic cells contributes to atherosclerosis progression. In this study, we found that hepatocyte-specific deletion of Ldlr in combination with high-fat, high-cholesterol diet feeding induced hypercholesterolemia and atherosclerosis in mice. On this background, further deletion of Ldlr in endothelial cells or smooth muscle cells had no significant effects on atherosclerosis, whereas myeloid-selective ablation of Ldlr markedly attenuated atherosclerotic plaque formation. The decreased percentages of T cells and natural killer T cells in the aorta of mice lacking Ldlr in myeloid cells partially explained the reduced atherosclerotic burden, despite that bone marrow-derived macrophages from Ldlr knockout mice could still be induced to form foam cells in vitro. Therefore, LDLR is better to be elevated in a cell-specific manner for cardiovascular disease prevention and treatment.