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. 2022 May 26;145(25):1853–1866. doi: 10.1161/CIRCULATIONAHA.122.059863

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© 2022 The Authors.

Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

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Figure 1. — Cardiac overexpression of IGF1R improves ejection fraction and effort tolerance in early adulthood, but causes heart failure and premature mortality late in life. A, Male mice with cardiomyocyte-specific overexpression of the human IGF1 receptor (IGF1R^tg) and their wild-type (WT) littermates (FVB/N background) were subjected to a comprehensive assessment of cardiac function and structure at the indicated age. B, Representative echocardiography-derived left ventricular (LV) M-mode tracings; C, LV mass normalized to body weight (BW); D, LV posterior wall thickness (LVPW); E, LV remodeling index (LVRI); F, heart rate (HR); and G, LV ejection fraction (LVEF) in 6-, 12-, and 20-month-old IGF1R^tg and WT mice (n=10 mice per group). H, Maximum workload during exercise tolerance testing in 3-, 12-, and 20-month-old IGF1R^tg and WT mice (n=5–6 mice per group). I, Body surface area–normalized cardiac output (cardiac index), derived by echocardiography, in IGF1R^tg and WT mice at the age of 6, 12, and 20 months (n=10 mice per group). J and K, Representative heart photomicrographs (J) and body surface area–normalized left atrial area (LAA_i; K) in 20-month-old IGF1R^tg and WT mice (n=10 mice per group). L, Maximum oxygen consumption (Vo₂max) during exercise tolerance testing in IGF1R^tg and WT mice at the age of 3, 12, and 20 months (n=5–6 mice per group). M, Lung weight normalized to tibia length (TL) in 20-month-old IGF1R^tg and WT mice (n=10 mice per group). N, Kaplan-Meier survival analysis of IGF1R^tg and WT mice (n=48/90 mice per group, respectively). Median survival is depicted by the dashed lines (please see also Table S3 for details). O, Maximum lifespan calculated as the average lifespan of the longest-lived decile in IGF1R^tg and WT mice (n=5/9 mice per group, respectively). P, Tumor incidence detected by gross necropsy in IGF1R^tg and WT mice (20/17 mice per group, respectively). Number in brackets indicates the number of mice that developed tumors. Indicated P values on top of panels (C–I and L) represent factor comparisons by 2-way ANOVA including genotype and age as fixed factors, followed by simple main effects analysis of pairwise comparisons between IGF1R^tg and their age-matched WT controls. Other P values were calculated by the Welch t test (K, M, and O) or χ² test (P). Bars and error bars show means and SEM, respectively, with individual data points superimposed. IGF1 indicates insulin-like growth factor 1; IGF1R, IGF1 receptor; and IGF1R^tg mice, mice overexpressing human IGF1R specifically in cardiomyocytes.