Journal: bioRxiv
Article Title: Immunoregulatory gene GIMAP6 suppresses lethal atherosclerotic vasculopathy and ischemic heart failure
doi: 10.64898/2026.01.26.701509
Figure Lengend Snippet: (A) Kaplan-Meier survival curves for Gimap6 − / − (males, n = 67; females, n = 60), Gimap6 +/ − (males, n = 41; females, n = 53), and Gimap6 +/+ (males, n = 35; females, n = 47) mice on a standard-fat diet (SFD). (B) Age at death (weeks) for male (n = 67) and female (n = 60) Gimap 6 − / − mice shown in (A). Each point represents an individual animal. (C) Representative images of gross heart anatomy from 5-month-old male wild-type (WT) and Gimap6 − / − mice. Scale bar, 0.5 cm. (D) Left: diagram of transverse heart sections. Right: 2,3,5-Triphenyltetrazolium chloride-stained sections from 7-month-old male WT and Gimap6 − / − mice appearing moribund (severely reduced activity, hunched posture, ruffled fur). Pale non-staining areas (black arrows) indicate infarcted tissue, viable myocardium stains red. The dashed black box highlights a 2.5x enlarged view of selected sections. Scale bar, 0.5 cm. (E) Heatmap displaying plasma cardiac troponin I (pg/mL) levels in individual WT (n = 11) and Gimap6 − / − (n = 13) SFD-fed mice measured from blood samples collected every 4 weeks between 8 and 24 weeks of age (n = 3–7 per time point, pooled from 3 independent experiments). Each row represents a single mouse. (F) Quantitation of plasma cardiac troponin I in male (n = 10) and female (n = 12) Gimap6 − / − mice appearing moribund compared to age- and sex-matched healthy WT controls (male, n = 5; female n = 6). Each dot represents an individual mouse. Bars indicate mean ± standard deviation (SD). (G) Representative Masson’s trichrome-stained transverse heart sections from 5-month-old male WT and Gimap6 − / − mice. The right ventricle (RV) and left ventricle (LV) are labeled. Healthy myocardium appears pink and asterisks (*) highlight fibrotic tissue (blue) indicating areas of potential prior infarcts. The magnified inset (6x) from the Gimap6 − / − heart further highlights the presence of inflammatory cell infiltrates (green arrow) and vascular abnormalities (yellow arrow) within the fibrotic regions. Scale bar, 0.25 cm. (H) Representative short-axis 2D M-mode echocardiograms from male WT and Gimap6 − / − mice at 22 weeks and female WT and Gimap6 − / − mice at 14 weeks. The overlaid curve (blue) traces the left ventricular internal diameter (LVID) with bars indicating systole (LVIDs, green) and diastole (LVIDd, red). (I) Ejection fraction (EF) values for WT and Gimap6 − / − mice computed from echocardiograms (n = 3 per group, per time point). (J) The corrected QT interval (QTc), and QRS wave duration measurements from male WT (n = 3) and Gimap6 − / − (n = 3) mouse hearts at 14, 18, and 22 weeks. Data are presented as mean ± SEM, with each dot representing an individual mouse. (K) Representative telemetry electrocardiogram (EKG) recordings from one female WT and one female Gimap6 − / − mouse. The WT tracing shows normal P-QRSJ-T waves. Gimap6 − / − recordings display progressive abnormalities over the 30-day observation period. Ventricular fibrillation (VF), ventricular tachycardia (VT). (L) Color Doppler echocardiogram of the aortic arch during diastole in 3.5-month-old WT and Gimap6 − / − male and female mice. Colors represent blood flow velocity: red indicates flow toward the transducer, blue indicates flow away from the transducer. The color scale represents velocity from −668 mm/s (blue) to +668 mm/s (red). Dotted boxes highlight regions of turbulent flow. (M) Representative en face images of Oil Red O (ORO)-stained aortae from cohoused 5-month-old male WT and Gimap6 − / − mice maintained on an SFD. Insets (1–4) show 3.5x magnified views of the indicated regions. Scale bar, 0.5 cm. Right: quantification of ORO-positive plaque area, expressed as a percentage of the total aortic surface area. Each point represents an individual animal. P values were calculated by log-rank (Mantel-Cox) test in (A), multiple unpaired t -tests, with the Holm-Šídák method used to correct for multiple comparisons in (I) and (J), or unpaired t -test in (B) (F) and (M). Statistical significance is denoted as not significant (ns), * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.
Article Snippet: Long-term cardiac monitoring was performed using surgically implanted ECG telemetry transmitters (Data Sciences International, ETA-F10) under sterile conditions.
Techniques: Staining, Activity Assay, Clinical Proteomics, Quantitation Assay, Standard Deviation, Labeling
