Figure 3. Inhibiting 12(S)-HETE/TRPV1 interaction improves vascular dysfunction and diminishes HFpEF manifestation.

(A) Carbamoylcholine (Cch) induced vasorelaxation in murine mesenteric resistance arteries preconstricted with 10⁻⁵M phenylephrine (Phe) was improved in diabetic Lepr^db/db after intravenous injections for 4 consecutive days of the V1-cal peptide, but not V1-scr, a scrambled version of V1-cal, compared to control mice. n=8–12 mice/group, Two-way ANOVA/Bonferroni, ***P<0.001 as indicated, n.s. not significant. (B) Pictures show representative murine resistance arteries and their response to Cch-induced vasorelaxation at 10⁻⁵M after preconstriction. Intravenous injection of V1-cal but not V1-scr improved (C) ratio between early-to-late stage (E/A) diastolic filling, (D) mitral wave E to E′ wave (E/E′) ratio and (E) left ventricular ejection fraction (LVEF) of LepR^db/db vs. LepR^db/+. n=6–10 mice/group, One-way ANOVA/Bonferroni, *P<0.05, **P<0.01 control or as indicated. (F) Representative pulsed-wave Doppler (PW-doppler, top) and tissue doppler imaging (TDI, bottom) tracings for data quantified in C-E. (G) V1-cal but not V1-scr increased capillary density in left ventricular cardiac tissue. Graph shows quantification of images in H for capillary density per mm² in LepR^db/+ vs. LepR^db/db with V1-scr or V1-cal treatment. 2 randomized areas were analysed per mouse by a blinded observer, n=4–5 mice/group, One-way ANOVA/Bonferroni, *P<0.05 as indicated. (H) CD31 immunofluorescence staining of murine heart sections showing CD31-positive (green) capillaries and DAPI-stained cell nuclei (blue). Scale bar indicates 10μm. All graphs show mean±SEM. DMT2 – type 2 diabetes mellitus, WT-wild type.