Factor Xa Inhibition with Apixaban Does Not Influence Cardiac Remodelling in Rats with Heart Failure After Myocardial Infarction

Graphical Abstract

Scheme 1. Schematic representation of the experimental protocol

Fig. 1. Effect of apixaban on cardiac function. a Representative LV sections stained with Masson’s trichrome. b Quantification of infarct size from Masson’s trichrome–stained section; n = 8–17/group. c Left ventricular internal dimensions in diastole (LVIDd) at week 11; n = 8–17/group. d Ejection fraction of the LV at week 11. e Longitudinal change of LV ejection fraction post-MI and before termination; n = 8–17/group. f Ratio of biventricular weight to tibia length; n = 8–17/group. Data are presented as means ± SEM. *p < 0.05 vs sham with the same treatment; ‡p < 0.05 vs MI—post-MI

Fig. 2. Effect of apixaban on cardiac histology and molecular markers for remodelling and fibrosis. a Quantification of cardiomyocyte cross-sectional area from WGA-stained section; n = 8–17/group. b Representative LV sections stained with WGA and Masson’s trichrome to assess cardiomyocyte hypertrophy and fibrosis. c Quantification of fibrosis in non-infarcted LV from Masson’s trichrome–stained section; n = 8–17/group. d, e Measurement of mRNA levels to assess molecular markers for remodelling and fibrosis in non-infarcted LV, respectively, normalized to 36b4; n = 8–17/group. Data are presented as means ± SEM. *p < 0.05 vs sham with the same treatment

Fig. 3. Effect of apixaban on PAR1 signalling pathways. a RhoA activity; n = 6/group. b Western blot analysis of PAR1, total and phosphorylated Akt; n = 6/group. c Quantification of PAR1 protein levels; n = 6/group. d Quantification of Akt phosphorylation protein levels; n = 6/group. Apix, apixaban. The density of each band was normalized to GADPH acting as a loading control and presented as fold change over Sham-veh group. Data are presented as means ± SEM. *p < 0.05 vs sham with the same treatment