Apoe-KO(2)

通过敲除Apoe基因exon 2-4，建立Apoe-KO(2)小鼠模型。原Apoe-KO(NM-KO-00033)小鼠模型因技术原因已下架。

Fig 1. Lipid profile biochemical markers of male Apoe-KO mice and  WT mice CD conditions. Under CD conditions, male Apoe-KO mice exhibit elevated levels of total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) compared to WT mice, while high-density lipoprotein cholesterol (HDL-C) levels are decreased. (n=5-10)

Abbr. WT, wild type; CD, chow diet.

Fig 2. Oil Red O staining of aortic valve in male Apoe-KO mice and WT mice under CD conditions. The results indicate that no lipid accumulation was observed in the aortic valves of WT mice at 7 months of age. In contrast, all Apoe-KO mice (6/6) exhibited significant lipid accumulation in the aortic valves as early as 5 months of age, with the severity of this phenotype progressively worsening with age. (n=4-6)

Abbr. WT, wild type; CD, chow diet.

Fig 3. Oil Red O staining of aorta in male Apoe-KO mice and WT mice under CD conditions. The results indicate that at 5 months of age, WT mice exhibit no significant lesions in the aorta, while some Apoe-KO mice (4/6) show fat accumulation near the aortic arch. By 6 to 7 months of age, all Apoe-KO mice (4/4) exhibit fat accumulation, with the severity of this phenotype progressively increasing. (n=4-6)

Abbr. WT, wild type; CD, chow diet.

Fig 4. Masson staining of aortic valve in Apoe-KO mice and WT mice under CD conditions. Muscle fibers appear red, while collagen fibers are stained blue. Apoe-KO mice exhibit increased collagen content within plaques, suggesting enhanced plaque stability. (n=3)

Abbr. WT, wild type; CD, chow diet.

Fig 5. Representative pictures of aortic valve. In WT mice, no significant plaque formation, necrosis, or inflammatory cell infiltration is seen. However, in Apoe-KO mice, extensive plaque formation is observed in the aortic valve, protruding into the lumen. Numerous interwoven collagen fibers are present, along with abundant infiltration of foam cells (red arrows). A small amount of cholesterol crystals (black arrows), appearing as needle-shaped voids, are visible, accompanied by minor deposits of brown pigment (green arrows). A small number of infiltrating lymphocytes (yellow arrows) are also noted. Myocardial cells display loose and irregular arrangement. The black box indicates the location of the magnified view.

Fig 6. The body weight curve of male Apoe-KO mice and WT mice under HFD conditions. (n=10-15)

Abbr. WT, wild type; HFD, high-fat diet.

Note. HFD started at 6 weeks of age.

Fig 7. Lipid profile biochemical markers of male Apoe-KO mice and WT mice under HFD conditions. Under HFD conditions, male Apoe-KO mice exhibit elevated levels of triglycerides (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) compared to WT mice, while high-density lipoprotein cholesterol (HDL-C) levels are decreased. (n=7-15)

Abbr. WT, wild type; HFD, high-fat diet.

Note. HFD started at 6 weeks of age.

Fig 8. Oil Red O staining of aortic valve in male Apoe-KO mice and WT mice under HFD conditions. The results indicate that no lipid accumulation was observed in the aortic valves of WT mice at 17 weeks of HFD. In contrast, all Apoe-KO mice (3/3) exhibited significant lipid accumulation in the aortic valves as early as 7 weeks of HFD, with the severity of this phenotype progressively worsened with age. (n=3-5)

Abbr. WT, wild type; HFD, high-fat diet.

Note. HFD started at 6 weeks of age.

Fig 9. Oil Red O staining of aorta in male Apoe-KO mice and WT mice under HFD conditions. The results indicate that after 17 weeks of HFD, WT mice exhibit no significant lesions in the aorta, while all Apoe-KO mice (3/3) show fat accumulation near the aortic arch after 7 weeks of HFD. By 17 weeks of HFD, the severity of this phenotype progressively increasing. (n=3-5)

Abbr. WT, wild type; HFD, high-fat diet.

Note. HFD started at 6 weeks of age.

Fig 10. Masson staining of aortic valve in Apoe-KO mice and WT mice under HFD conditions. Muscle fibers appear red, while collagen fibers are stained blue. Apoe-KO mice exhibit increased collagen content, suggesting enhanced plaque stability. (n=3)

Abbr. WT, wild type; HFD, high-fat diet.

Note. HFD started at 6 weeks of age.

Fig 11. Representative pictures of aortic valve. In WT mice after 17 weeks of HFD feeding, the vascular intima of cardiac tissue appears smooth with no plaque formation. Myocardial cells are loosely arranged, and occasional perivascular lymphocyte infiltration is noted (red arrows). In contrast, ApoE-KO mice after 7 week of HFD feeding display extensive plaques (yellow arrows) within the vessels, protruding into the lumen, with fibrous connective tissue (brown arrows) and minimal foam cell accumulation (blue arrows) on the surface. Needle-like clefts (orange arrows), likely cholesterol crystals, and necrotic debris (black arrows) are seen within the plaques. Lymphocyte infiltration (red arrows) and fibrous tissue proliferation (purple arrows) are present in the interstitial space. The black box indicates the magnified region.

Abbr. WT, wild type; HFD, high-fat diet.

Note. HFD started at 6 weeks of age.

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity
来源杂志：Cell Reports