Fig. 1 | Communications Biology

Fig. 1

From: SR9009 administered for one day after myocardial ischemia-reperfusion prevents heart failure in mice by targeting the cardiac inflammasome

Fig. 1The alternative text for this image may have been generated using AI.

Short-term pharmacological targeting of REV-ERB after mI/R protects against HF. a Experimental design, left anterior descending coronary artery ligation for 45 min of ischemia followed by reperfusion and SR9009 treatment (i.p. once daily at ZT06 for up to 5 days), and pathophysiologic assessments up to 8 weeks post-mI/R. b All infarcts were reproducibly similar within the first day post-mI/R, as quantified by area at risk:left ventricle (AAR:LV), infarct area:LV (IN:LV), and infarct area:area at risk (IN:AAR) (n = 5 hearts/group). c mI/R mice treated with SR9009 for just 5 days had reduced heart weight (HW) and HW:body weight (BW) vs. mI/R+vehicle controls, at 8 weeks post-mI/R (see Table 1 for details). *p < 0.01 mI/R+SR9009 vs. mI/R+vehicle. d Functional benefits of short-term SR9009 treatment after mI/R include smaller LV diastolic (LVIDd) and systolic (LVIDs) dimensions and better % ejection fraction (% EF) and % fractional shortening (% FS), as compared with mI/R+vehicle, by echocardiography over 8 weeks post-mI/R (see Table 1 for all echocardiography values). *p < 0.0001 mI/R+SR9009 vs. mI/R+vehicle. e Preserved normal pressure–volume (PV) dynamics in SR9009-treated mI/R mice, as compared with mI/R+vehicle, representative image (see Table 1 for all hemodynamics values). f Representative hearts showing cardiac morphology in sham (top panel) and mI/R mice. The SR9009-treated mI/R hearts have less hypertrophy (less equidistant sections; middle panels), as compared with mI/R+vehicle mice (more equidistant sections; bottom panels). Heart sections are collected every 300 µm. Sections are stained with Masson’s trichrome. g The LV wall of sections #5 (s5) and #6 (s6) (from Fig. 1f) are shown with increased magnification to highlight comparisons in the infarct region. Top panel, normal LV wall in sham mice. Middle panel, transmural infarct in LV wall of mI/R hearts, as indicated by the blue-staining region. Bottom panel, animals treated short-term with SR9009 after mI/R have reduced infarct expansion by 8 weeks after mI/R. Scale bar (top right of each paired image) = 500 μm. h Quantification demonstrating that there is significantly (*p < 0.001) less infarct volume and infarct expansion in the SR9009-treated hearts by 8 weeks post-mI/R

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