Figure 1

Overexpression of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) prevents the development of angiotensin II-induced abdominal aortic aneurysm (AAA) and reduces the mortality and severity in Apoe^−/− mice. (A) Experimental design. Twelve-week-old apolipoprotein E-deficient (Apoe^−/−) mice or CTLA-4-Tg/Apoe^−/− mice fed a high-cholesterol diet were infused with angiotensin II or saline for 28 days and were euthanized at 16 weeks of age for evaluation of AAA formation. Apoe^−/− mice infused with angiotensin II or saline served as controls. (B) Kaplan-Meier curve shows survival rate in angiotensin II-infused Apoe^−/− (n = 40) and CTLA-4-Tg/Apoe^−/− (n = 35), or saline-infused Apoe^−/− (n = 5) and CTLA-4-Tg/Apoe^−/− (n = 5) mice. *P < 0.05; **P < 0.01; log-rank (Mantel-Cox) test. (C) Mortality due to AAA rupture in angiotensin II-infused Apoe^−/− (n = 40), CTLA-4-Tg/Apoe^−/− (n = 35) mice. *P < 0.05; chi-squared test. (D) Representative photographs displaying macroscopic features of aneurysms induced by angiotensin II. None of the animals infused with saline developed aneurysm. Arrowheads indicate abdominal aneurysms. (E) Severity of aneurysm in angiotensin II-infused Apoe^−/− (n = 40) and CTLA-4-Tg/Apoe^−/− (n = 35). (F) Maximal diameter of abdominal aorta in angiotensin II-infused Apoe^−/− (n = 20) and CTLA-4-Tg/Apoe^−/− (n = 26). Data points represent individual animals. Horizontal bars represent means. Error bars indicate s.d. *P < 0.05; Mann-Whitney U-test. Ang-II, angiotensin II.