Fig. 1: Nitro-oleic acid mitigates heart failure in mice with HFpEF.
Mice received a high-fat diet (HFD) and the endothelial nitric oxide synthase inhibitor L-NAME (HFD + L-NAME) or a standard chow diet (Chow) for 15 weeks (wk). They were treated with vehicle or nitro-oleic acid (NO2-OA) during the last 4 wk. Echocardiography (Echo), glucose tolerance test (GTT), hemodynamics (PV-loop), exercise, transmission electron microscopy (TEM), proteomics of left ventricular tissue (LV proteome) and respirometry of isolated cardiomyocytes was conducted at the final time point. a Experimental protocol. b Left ventricular ejection fraction (LVEF) and left ventricular posterior wall thickness (LVPW, d) (N = 19/14/18). c Representative ultrasound images of 4-chamber B-Mode (upper panel) and LV tissue doppler at mitral annulus (lower panel) to assess diastolic function. d Ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (MV E/e´) and isovolumetric relaxation time (IVRT) (N = 19/14/18). e LV global longitudinal strain (GLS) (N = 9/9/9). f Compliance index shown as E/e´ in ratio to the individual end diastolic volume (EDV) (N = 19/14/18). g, h LV end-diastolic pressure (LV EDP) (g) and chamber stiffness index ßW (h) derived from hemodynamic mesurements (N = 11/7/6). i Work rate calculated from maximum exhaustion exercise test (N = 18/14/17). j Left atrial area (LA area) (N = 19/14/18). k Representative images of muscularization of pulmonary arteries by staining α-smooth muscle actin (αSMA) and von Willebrand factor (vWF) (left) and quantification of αSMA-positive area related to vessel circumference of arterioles (right) (N = 9/8/9). l LV arterial elastance (LV Ea) (N = 11/7/6). Data are presented as mean ± standard deviation. Statistical significance was calculated by One-way ANOVA followed by Bonferroni´s post-hoc test for b, d, e, g-l. Statistical significance for f was calculated by Kruskal-Wallis-test followed by Dunn´s multiple comparison test. Only statistically significant differences are indicated. p*<0.05, **<0.01, ***<0.001, ****<0.0001.
