Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice

Figures

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  Figure 1.. FXR expression in cardiac tissue. (A) FXR protein expression levels were assessed using western blot analysis. Tissue samples from infarct regions of WT mice that underwent MI and from corresponding regions of sham-operated WT mice were collected at various time points post-surgery (n=5/time point). (B) Western blot analysis results were semi-quantified and normalized to GAPDH. Data are expressed as the mean ± standard error of the mean. *P<0.05 vs. the sham group. FXR, farnesoid X receptor; WT, wild type; MI, myocardial infarction.

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  Figure 2.. Cardiac structure and function in mice following MI. (A) Representative photographs of cardiac tissue captured 4 weeks post-MI revealed preservation of LV wall integrity and reduced LV chamber size in FXR−/− mice (n=7). (B) Triphenyl tetrazolium chloride staining performed on day 28 following MI was used to calculate the infarct/LV area ratio in FXR−/− and WT mice. (C) Infarct size assessed 4 weeks post-MI was significantly larger in WT compared with FXR−/− mice (n=4/group). Data are expressed as the mean ± standard error of the mean. *P<0.05 vs. the WT group. MI, myocardial infarction; LV, left ventricle; FXR, farnesoid X receptor; WT, wild type.

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  Figure 3.. Decreased interstitial fibrosis and increased microvesicular density in the peri-infarct border zone of FXR−/− mice 4 weeks following MI. (A) Representative photomicrographs (×100 and ×200 magnification) of serial sections stained with hematoxylin and eosin for the morphological identification of the border zone and infarct areas. (B) Representative photomicrographs (×100 and ×200 magnification) of Massons trichrome-stained sections, captured on week 4 following MI, reveal interstitial fibrosis in the border zone in WT and FXR−/− mice. (C) Representative photomicrographs (×100 and ×200 magnification) of sections from the infarcted LV regions of WT and FXR−/− mice stained for α-smooth muscle actin. (D) Representative photomicrographs (×200 and ×400 magnification) of cardiac sections from WT and FXR−/− mice stained with anti-cluster of differentiation 31 on day 28 following MI. mRNA expression levels of (E) collagen III and (F) MMP-9 in LV tissue samples were assessed using reverse transcription-quantitative polymerase chain reaction and normalized to GAPDH expression on day 28 following MI. Data are expressed as the mean ± standard error of the mean (n=6 mice/group). *P<0.05 vs.…

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  Figure 4.. (A) TUNEL assay on day 7 following MI revealed an increase in cardiomyocyte apoptosis in WT vs. FXR−/− mice. Magnification, ×200. (B) The ratio of apoptotic/non-apoptotic myocyte was significantly higher in WT mice compared with FXR−/− mice on day 7 following MI (n=3 mice/group, 5 fields/heart). (C) Representative western blot demonstrating cleaved caspase-3 protein expression levels in infarct regions of sham- and MI-operated WT and FXR−/− mice on day 7 following MI. (D) Relative protein expression levels of cleaved caspase-3 were semi-quantified and normalized to GAPDH. Data are expressed as the mean ± standard error of the mean (n=4 mice/group). *P<0.05 vs. the WT + MI group. FXR, farnesoid X receptor; MI, myocardial infarction; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labelling; WT, wild type.