Table 1.
Prevention Experiments | Aortic Tx Recipientsa—Fed HFD 6 to 14 wk (n=6 per group) | Single Injectiona—Fed HFD 6 to 12 wk (n=6 per group) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
BL/6 | CD31‐TFPI‐Tg | P Valueb | BL/6 | CD31‐Hir‐Tg | P Valueb | PBS | HLL (5 μg/g) | PTL060 (2.5 μg/g) | PTL060 (5 μg/g) | PTL060 (10 μg/g) | P Valuec | |
Body mass | ||||||||||||
Age 6 wk | 18.6±0.27 | 18.6±0.25 | 0.99 | 19.6±0.42 | 19.6±0.31 | 0.99 | 19.0±0.40 | 19.4±0.22 | 19.4±0.44 | 19.4±0.38 | 19.2±0.24 | 0.87 |
End of experiment | 25.2±1.71 | 24.6±1.36 | 0.63 | 26.8±0.34 | 25.9±0.77 | 0.99 | 32.0±1.63 | 32.0±0.99 | 31.4±0.84 | 29.8±0.35 | 29.4±0.73 | 0.36 |
Cholesterol, mmol/L | 53.1±3.31 | 52.9±3.67 | 0.99 | 50.1±4.98 | 50.2±5.77 | 0.99 | 51.0±5.56 | 54.1±5.70 | 49.3±4.56 | 50.3±4.36 | 50.1±5.44 | 0.97 |
Triglycerides, mmol/) | 2.1±0.14 | 2.0±0.20 | 0.99 | 2.0±0.13 | 2.0±0.14 | 0.99 | 2.1±0.31 | 2.1±0.36 | 2.2±0.28 | 2.2±0.27 | 2.1±0.30 | 1.00 |
HDL, mmol/L | 1.5±0.11 | 1.5±0.10 | 0.99 | 1.6±0.07 | 1.5±0.08 | 0.99 | 1.4±0.28 | 1.5±0.08 | 1.6±0.12 | 1.5±0.09 | 1.5±0.09 | 0.92 |
LDL, mmol/L | 57.2±2.73 | 55.2±3.49 | 0.97 | 63.9±9.97 | 61.0±6.28 | 0.92 | 55.6±6.64 | 54.7±4.48 | 54.1±4.72 | 51.7±5.89 | 52.8±5.42 | 0.99 |
Regression Experiments | 6‐wk‐old | Series 1 HFD 6 to 28 wks (n=6 per group) | Series 2 HFD 6 to 28 wk (n=6 per group) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baselined | PBSe | Tail Only | PTL060 (10 μg/g) | P Valuec | Baselined | PBS | HLL (5 μg/g) | PTL060 (5 μg/g) | PTL060 (10 μg/g) | P Valuec | ||
Body mass | ||||||||||||
Age 6 wk | ··· | 19.3±0.28 | 19.6±0.37 | 19.1±0.15 | 19.3±0.38 | 0.74 | 20.2±0.39 | 20.1±0.38 | 20.6±0.07 | 20.1±0.30 | 20.3±0.26 | 0.73 |
Age 22 wk | ··· | 30.5±0.58 | 32.8±0.44 | 30.4±0.90 | 32.0±0.81 | 0.19 | 31.5±1.34 | 31.4±0.84 | 31.1±0.66 | 31.2±1.00 | 31.9±0.78 | 0.85 |
End of experiment | ··· | ··· | 33.2±0.31 | 31.8±0.73 | 28.7±1.55 | 0.03 | ··· | 32.9±1.19 | 31.4±0.33 | 30.2±0.93 | 29.8±0.59 | 0.11 |
Cholesterol, mmol/L | 10.3±4.6 | 56.7±6.08 | 61.5±6.51 | 61.9±6.35 | 57.9±3.61 | 0.88 | 54.9±6.25 | 56.9±6.93 | 54.1±5.39 | 53.9±6.31 | 54.3±13.1 | 0.41 |
Triglycerides, mmol/L | 0.36±0.14 | 2.08±0.15 | 2.25±0.11 | 2.49±0.13 | 2.19±0.16 | 0.26 | 2.27±0.28 | 1.68±0.31 | 2.21±0.38 | 2.2±0.33 | 2.16±0.69 | 0.86 |
HDL, mmol/L | 4.46±1.1 | 1.54±0.007 | 1.49±0.06 | 1.46±0.06 | 1.56±0.06 | 0.65 | 1.61±0.12 | 1.58±0.11 | 1.78±0.2 | 1.6±0.16 | 1.68±0.38 | 0.27 |
LDL, mmol/L | 14.4±2.8 | 46.5±3.39 | 56.1±2.92 | 57.4±2.57 | 50.8±2.84 | 0.07 | 53.8±3.51 | 62.7±4.43 | 63.5±3.55 | 60.6±6.79 | 63.3±16.7 | 0.97 |
“n” refers to number of animals per group. Samples from each animal were analyzed in triplicate. BL/6 indicates C57BL/6J; HDL, high‐density lipoprotein; HFD, high‐fat diet; HLL, hirulo analogue chemically modified to accept the myristoyl tail (Please note: HLL 5 μg is equimolar to PTL060 10 μg); LDL, low‐density lipoprotein; and TFPI, tissue factor pathway inhibitor.
In prevention experiments, aortic transplants performed, and single injections given to mice aged 8 weeks, 2 weeks after starting a high‐fat diet.
Two‐way ANOVA for multiple groups.
One‐way ANOVA for multiple groups (NB: values from 6‐week‐old mice not included in comparisons).
Baseline=week 22. Mice in the “baseline” groups were harvested at this timepoint before any treatment.
Treatments given weekly by intravenous injection for 6 weeks (mice aged 22–28 weeks).