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. 2017 Jul 20;2(14):e93735. doi: 10.1172/jci.insight.93735

Figure 7. Restoration of IGF-1 reduces circulating growth hormone levels and attenuates atherosclerotic plaque burden in L-Jak2–/–ApoE–/– mice.

Figure 7

To restore circulating IGF-1 levels by pharmacologic means, vehicle (saline + 10 mmol/L HCl) or human long R3 IGF-1 (1.0 mg/kg/d), a biologically active IGF-1 analog, was administered by s.c. osmotic pumps into 8-week-old L-Jak2–/–ApoE–/– mice and L-Jak2+/+ApoE–/– littermate controls for 12 weeks while being fed an atherogenic diet containing 0.2% cholesterol. (A) Serum growth hormone (GH) levels were measured in vehicle-infused L-Jak2+/+ApoE–/– (n = 7), IGF-1–infused L-Jak2+/+ApoE–/– (n = 4), vehicle-infused L-Jak2–/–ApoE–/– (n = 7), and IGF-1–infused L-Jak2–/–ApoE–/– (n = 6) mice. (B) Representative photographs of en face oil red O (ORO) staining and quantification of atherosclerotic plaque area in descending aortas of vehicle-infused L-Jak2+/+ApoE–/– (n = 7), IGF-1–infused L-Jak2+/+ApoE–/– (n = 4), vehicle-infused L-Jak2–/–ApoE–/– (n = 8), and IGF-1–infused L-Jak2–/–ApoE–/– (n = 6) mice. Scale bar: 1 cm. (C) Representative images of longitudinal sections from the aortic arch of vehicle-infused L-Jak2+/+ApoE–/– (n = 6), IGF-1–infused L-Jak2+/+ApoE–/– (n = 4), vehicle-infused L-Jak2–/–ApoE–/– (n = 8), and IGF-1–infused L-Jak2–/–ApoE–/– (n = 5) mice stained with H&E and quantification of lesion size at the lesser curvature. B, brachiocephalic artery; C, left common carotid; S, subclavian artery; L, lesser curvature. Scale bar: 200 μm. (D) Representative images of the lesser curvature of longitudinal aortic arch sections from vehicle-infused L-Jak2+/+ApoE–/– (n = 5), IGF-1–infused L-Jak2+/+ApoE–/– (n = 2), vehicle-infused L-Jak2–/–ApoE–/– mice (n = 8), and IGF-1–infused L-Jak2–/–ApoE–/– (n = 5) mice immunostained with antibody against Mac-3 and quantification of positively stained area. Scale bar: 100 μm. To restore circulating IGF-1 using a genetic approach, L-Jak2–/–ApoE–/– and L-Jak2+/+ApoE–/– controls expressing an Igf1 transgene in the liver (L-Jak2–/–ApoE–/–Tg-Igf1+ or L-Jak2+/+ApoE–/–Tg-Igf1+, respectively) and those not expressing the transgene (L-Jak2–/–ApoE–/–Tg-Igf1– or L-Jak2+/+ApoE–/–Tg-Igf1–, respectively) were fed an atherogenic diet containing 0.2% cholesterol for 13–14 weeks, starting at 8 weeks of age. (E) Representative photographs of en face ORO staining and quantification of atherosclerotic plaque area in descending aortas of L-Jak2+/+ApoE–/–Tg-Igf1– (n = 7), L-Jak2+/+ApoE–/–Tg-Igf1+ (n = 9), L-Jak2–/–ApoE–/–Tg-Igf1– (n = 8), and L-Jak2–/–ApoE–/–Tg-Igf1+ (n = 11) mice. (F) Serum GH levels were measured in L-Jak2+/+ApoE–/–Tg-Igf1– (n = 4), L-Jak2+/+ApoE–/–Tg-Igf1+ (n = 5), L-Jak2–/–ApoE–/–Tg-Igf1– (n = 3), and L-Jak2–/–ApoE–/–Tg-Igf1+ (n = 8) mice. In each of the panels, each dot in the scatter plot indicates an individual animal. Data represent mean ± SEM. Differences between groups were analyzed for statistical significance using One-way ANOVA with Newman-Keuls post-hoc test. *P < 0.05, ***P < 0.001.