Figure 1 Brachiocephalic artery of ApoE KO/Tg mouse 20 weeks on high fat diet. Verhoeff-Van Gieson stain. Example of Grade 2 plaque with necrotic core containing cholesterol clefts. Arrow indicates IEM disruption.

Figure 2 Brachiocephalic arteries of ApoE KO mice 40 weeks on high fat diet. Arrow indicates (A) chondrocyte-like cells or (B) calcification.

Figure 3 Brachiocephalic arteries of ApoE KO/Tg mice 40 weeks on high fat diet. (A,C) Hematoxylin & Eosin. (B,D) Immunohistochemistry for macrophages (F4/80)

Figure 4Summary of the effect of PAPP-A overexpression in arterial smooth muscle on atherosclerotic plaque morphology in ApoE KO mice.

Lumin

Thrombus (0 = no, 1 = yes)
Thrombus (0 = not applicable, 1 = platelet/fibrin, 2 = red cell, 3 =
both 1 & 2)

Intima

Plaque (0 = absent, 1 = eccentric, 2 = concentric, 3 = both 1 & 2)
Plaque grade (1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 >75% of
luminal obstruction)
Surface erosion/fissure (0 = absent, 1 = present)
Fibrous cap (1 = thick, 2 = thin, 3 = absent)
Foam cells without fibrous cap (0 = absent, 1 = present)
Foam cells within the fibrous cap (0 = absent, 1 = present)
Foam cells beneath cap (0 = absent, 1 = present)
Other plaque cells (0 = absent, 1 = chondrocyte-like)
Necrotic core of plaque (0 = absent, 1 = present)
Calcification (0 = absent, 1 = present)
Plaque inflammation (0 = absent, 1 = chronic, 2 = acute, 3 = both
1 and 2)
Plaque hemorrhage (0 = absent, 1 = present)
Plaque progression (0 = absent, 1 = present)

Internal Elastic Membrane (IEM)

Fragmentation/disruption (0 = absent, 1 = present)

Media

Thinning under the plaque (0 = absent, 1 = present)
Thickening under the plaque (0 = absent, 1 = present)
Hypertrophy opposite the plaque (0 = absent, 1 = present) 

Adventitia

 Inflammation (0 = absent, 1 = chronic, 2 = acute, 3 = both 1 and 2)

Table 1: Spreadsheet key for morphological analysis of brachiocephalic arteries in atherogenic mice.

                                                                Grams

 

Start   

20 weeks

40 weeks

Males

ApoE KO

28.7 + 0.79     

48.9 + 3.39

52.1 + 4.67

ApoE KO/Tg 

26.1 + 0.81

 44.3 + 3.29

50.4 + 4.51

Females

ApoE KO                                             

22.1 + 0.55

35.9 + 3.69

41.0 + 5.72

ApoE KwO/Tg                                    

21.0 + 0.45     

32.5 + 2.05

43.6 + 5.77

Table 2: Body weights of ApoE KO and ApoE KO/PAPP-A Tg mice at 7 weeks-of-age and after 20 weeks and 40 weeks of high fat diet.

 

% of Mice

 

ApoE KO (21)

ApoE KO/Tg (18)

Plaque Grade

 

 

    1

45%

12%

    2

45%

25%

    3

--

52%

    4

9%

--

Necrotic Core

9%

75%*

IEL Disruption

55%

50%

Chondrocyte-like Cells

18%

--

Calcification

--

--

Plaque Inflammation

--

--

Plaque Progression

--

25%

Adventitial Inflammation

--

--

Table 3: Results from (N) mice are expressed as % of mice with the indicated morphology. *P = 0.002

 

% of Mice

 

ApoE KO (14)

ApoE KO/Tg (14)

Plaque Grade

 

 

    1

7%

--

    2

57%

36%

    3

14%

64%

    4

14%

--

Necrotic Core

100%

100%

IEL Disruption

57%

79%

Chondrocyte-like Cells

93%

64%

Calcification

43%

43%

Plaque Inflammation

7%

29%‡

Plaque Progression

29%

64%‡

Adventitial Inflammation

29%

29%

Table 4: Results from (N) mice are expressed as % of mice with the indicated morphology. ‡P = 0.07