Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: Ob-ZSF1 rats were randomized on E/e’ parameter from doppler echocardiographic analysis. For adult animal study, Le-ZSF1-CTRL N = 9, Ob-ZSF1-CTRL N = 11 and Ob-ZSF1-SAR247799 N = 11. For aged animals study Le-ZSF1-CTRL N = 9, Ob-ZSF1-CTRL N = 7 and Ob-ZSF1-SAR247799 N = 7; N = number of rats.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques:

Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: Diastolic function was evaluated by (A) E/e’ ratio (B) septal peak e’ wave velocity at mitral annulus level and (C) mitral valve peak E wave velocity. Cardiac systolic function was assessed by (D) ejection fraction, (E) end-diastolic volume, (F) end-systolic volume, (G) stroke volume and (H) cardiac index. Data are expressed mean ± SEM, except E, e’, E/e’, end-systolic volume, stroke volume and which are expressed as median ± IQR. † p<0.05, ††† p<0.001: comparison of Le-ZSF1-CTRL to Ob-ZSF1-CTRL using a Student t-test except for E/e’ and stroke volume for adult animals and for E wave for aged animals for which a Wilcoxon test was performed. ‡ p<0.05, ‡‡ p<0.01: p-values obtained from the comparison between Ob-ZSF1-CTRL and Ob-ZSF1-SAR247799 using a Student t-test except for E/e’ for adult animals and for E wave for aged animals for which a Wilcoxon test was performed. For adult animals, Le-ZSF1-CTRL N = 9, Ob-ZSF1-CTRL N = 11 and Ob-ZSF1-SAR247799 N = 11. For aged animals Le-ZSF1-CTRL N = 8–9, Ob-ZSF1-CTRL N = 6–7 and Ob-ZSF1-SAR247799 N = 7; N = number of rats. A lower number of n values is due to technical issue in echocardiography data acquisition.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques:

Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: (A) Heart weight/tibia length, (B) left atrial weight/tibia length, (C) right atrial weight/tibia length, (D) interventricular septum thickness at end-diastole (IVSd), (E) interventricular septum thickness at end-systole (IVSs), (F) left ventricular posterior wall thickness at end-diastole (LVPWd), (G) left ventricular posterior wall thickness at end-systole (LVPWs). Data expressed as mean ± SEM, except IVSd and LVPWd which are expressed as median ± IQR. †† p<0.01, ††† p<0.001: comparison of Le-ZSF1-CTRL to Ob-ZSF1-CTRL using a Student t-test, except LVPWd (adult animals) for which a Wilcoxon test was performed. ‡ p<0.05, ‡‡ p<0.01, ‡‡‡ p<0.001: comparison between Ob-ZSF1-CTRL and Ob-ZSF1-SAR247799 using a Student t-test, except LVPWd (adult animals) for which a Wilcoxon test was performed. For adult animals, Le-ZSF1-CTRL N = 9, Ob-ZSF1-CTRL N = 11 and Ob-ZSF1-SAR247799 N = 10–11. For aged animals Le-ZSF1-CTRL N = 8–9, Ob-ZSF1-CTRL N = 6–7 and Ob-ZSF1-SAR247799 N = 7; N = number of rats. A lower number of n values is due to technical issue in echocardiography data acquisition.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques:

Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: (A) perivascular collagen, (B) interstitial collagen, (C) representative histological images of cardiac fibrosis in Le-ZSF1-CTRL (I.), Ob-ZSF1-CTRL (II.) andOb-ZSF1-SAR247799 (III.), scale bar 5 mm and corresponding perivascular fibrosis (IV., V. and V.,) stained in green by Masson trichrome staining, scale bar, 100 μm. (D) microvascular density. Scatter plot showing relationships between (E) perivascular collagen and diastolic dysfunction (E/e’), (F) perivascular collagen and heart weight/ tibia length (normalized cardiac hypertrophy), (G) diastolic dysfunction (E/e’) and heart weight/ tibia length. For (A, B and D) data presented as mean ± SEM. † p<0.05: p-values obtained to compare Le-ZSF1-CTRL to Ob-ZSF1-CTRL using a Student t-test. ‡‡‡ p<0.001: p-values obtained from the comparison between Ob-ZSF1-CTRL and Ob-ZSF1-SAR247799 using a Student t-test. Le-ZSF1-CTRL N = 9, Ob-ZSF1-CTRL N = 7 and Ob-ZSF1-SAR247799 N = 7; N = number of rats.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques: Staining

Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: A) systolic blood pressure (SBP), (B) diastolic blood pressure, (C) representative spectra of systolic blood pressure variability showing very low frequency (VLF), low frequency (LF) and high frequency (HF) bands. (D) very low frequency (n.u.) bands from spectral analysis of SBP variability. Data presented as mean ± SEM, except SBP who is presented as median ± IQR. * p<0.05, ** p<0.01: p-values obtained to compare Le-ZSF1-CTRL to Ob-ZSF1 (Ob-ZSF1-CTRL and Ob-ZSF1-SAR247799 pooled) using a Student t-test. A Student t-test was also performed to compare Ob-ZSF1-CTRL to Ob-ZSF1-SAR247799 at baseline. No significant difference was observed between the two randomized groups at baseline for any of the parameters. † p<0.05: p-values obtained to compare Le-ZSF1-CTRL to Ob-ZSF1-CTRL using a Student t-test. ‡ p<0.05: p-values obtained from the comparison between Ob-ZSF1-CTRL and Ob-ZSF1-SAR247799 using a Student t-test except for SBP for which a Wilcoxon test was performed. For adult animals, Le-ZSF1-CTRL N = 8, Ob-ZSF1-CTRL N = 8 and Ob-ZSF1-SAR247799 N = 7; N = number of rats. The lower number of n values is due to technical issue in telemetry data acquisition.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques:

Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: Renal function and physiological parameters at baseline and after 4 weeks of treatment.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques:

Journal: PLoS ONE

Article Title: A G-protein-biased S1P 1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

doi: 10.1371/journal.pone.0257929

Figure Lengend Snippet: Comparison of the protective effects of SAR247799 in aged obese ZSF1 rats with effects seen in prior experimental systems.

Article Snippet: Ob-ZSF1 rats were randomized based on the E/e’ value to a control chow diet (Ob-ZSF1-CTRL N = 7) or to a diet with chow supplemented with 0.025% (w/w) SAR247799 (Ob-ZSF1-SAR247799 N = 7), (SSNIFF Spezialdiäten GmbH).

Techniques: Concentration Assay, Staining