Fig. 4

Improved cardiometabolic features in DKO mice. Mouse aortic rings preconstricted with U-46,619 were treated with cumulative addition of (A) acetylcholine (Ach) or (B) sodium nitroprusside (SNP) to induce relaxation. Relaxation values are expressed as percentage of the initial U-46,619-induced contraction. Data represent mean values ± SEM of 19–20 aortic rings per genotype isolated from 5 LdlrKO and 5 DKO mice; *p < 0.05, **p ≤ 0.01, ***p ≤ 0.001. (C) Axial stress versus axial stretch behavior (n = 3) and (D) circumferential stretch at 100 mmHg intramural pressure (n = 3). Data represent mean values ± SD. *p < 0.05; ** p ≤ 0.01. Representative transmission electron micrographs from the aortic arch of (E) LdlrKO and (F) DKO mice. (E) Residuals of elastic fibers (asterisk), smooth muscle cells (smc), and collagen fibers (cf.) in LdlrKO mice. (F) Normal elastic fibers (ef), smooth muscle cells, and collagen fibers in close proximity to elastic fibers in DKO mice. Scale bars, 2 μm. (G) Volcano plot showing selected upregulated (red) and downregulated proteins (blue) in DKO aortas reported to play a role in either inflammatory processes, atherogenesis, and/or vascular dysfunction in aortas. (H) Ingenuity Pathway Analysis (IPA) from nontargeted proteomics data of aortas showing downregulated protein sets (z-score < 2 in light blue; z-score > 2 in dark blue) and upregulated gene sets (red) in DKO mice. Figures represent data from 6 LdlrKO and 6 DKO mice