Abstract 146: Endothelin-1 Inoculation Attenuates Aortic Atherosclerosis in Rabbits under Cholesterol Rich Diet
Introduction The atherogenic potential of Endothelin-1 (ET1) has been extensively recognized and studied as a possible therapeutic target. However, the effects of an immunologic blockade of ET1 are unknown.
Hypothesis Our hypothesis was that the induction of an immunological response through subcutaneous inoculation of Endothelin-1 prevents atherosclerosis in rabbits exposed to a cholesterol rich diet (CRD) for 36 weeks.
Methods Eighteen New Zealand rabbits were divided in 4 different groups. Group A: 4 rabbits received CRD only. Group B: 5 rabbits were pre-treated with subcutaneous inoculation of ET1 (20 mg) plus Freund’s adjuvant (administered in 3 doses, 15 days apart) and then received CRD. Group C: 5 rabbits were pre-treated with subcutaneous inoculation of ET1 (20 mg) plus Montanide ISA 16 adjuvant (same schedule) and then received CRD; and group D: 4 rabbits received normal diet and no ET1 injection (control group). After 16 weeks, one rabbit in each group (A, B and C) and 2 rabbits in the control group were sacrificed. The rest of the animals were sacrificed after completing 36 weeks. An aortic extraction was done and pathologic slices prepared for hystomorphologic measurements, including vessel, lumen, and plaque area. Plaque/vessel area, plaque/lumen area, and plaque/lumen perimeter ratios, were also calculated.
Results Compared with rabbits that received CRD alone, rabbits that were pre-treated with subcutaneous inoculation of ET1 plus Freund’s adjuvant had an statistically significant difference in the plaque area (0.9 ± 0.9 vs. 0.2 ± 0.3 mm2, p=0.03), plaque perimeter (2.4 ± 2.0 vs. 0.8 ± 1.1 mm2, p=0.04), plaque width (0.4 ± 0.3 vs. 0.2 ± 0.2 mm2, p=0.02), and calculated ratios (p<0.04) at 16 weeks. The difference was more significant after 36 weeks, with plaque area (1.3 ± 1.1 vs. 0.27 ± 0.5 mm2, p<0.001), plaque perimeter (4.6 ± 2.4 vs. 1.4 ± 1.5 mm2, p<0.001), plaque width (0.4 ± 0.2 vs. 0.2 ± 0.1 mm2, p<0.001), and calculated ratios (p<0.014). This gruop of rabbits also had the highest anti-ET1 antibody titers (1/12800).
Conclusions Our findings suggest that the pre-treatment with subcutaneous inoculation of Endothelin-1 significantly attenuates aortic atherosclerosis in New Zealand rabbits exposed to a cholesterol rich diet for 16 to 36 weeks.
- © 2013 by American Heart Association, Inc.