Figure 7.

The canonical GLP-1 (glucagon-like peptide-1) receptor expressed on endothelial cells is essential for cardiovascular protection by liraglutide (Lira). A, In endothelial cell–specific GLP-1 receptor knockout mice (Glp1r^flox/floxxCdh5^cre, Glp1r ec^−/−), mRNA expression of the Glp1r was measured in isolated mouse lung endothelial cells (MLECs) and expression levels are shown in relation to the background strain (Cdh5^cre mice). Student t test; N=4 animals per group. B, Vascular function was evaluated by endothelium-dependent (acetylcholine [ACh]) relaxation of aortic rings (isometric tension studies). Two-way ANOVA and Bonferroni multiple comparison test; N=20–30 animals per group. C, Systolic blood pressure in mice was determined by noninvasive blood pressure recording on day 6 of ATII (angiotensin II) infusion. D, Representative (out of 3–4) Sirius red staining of aortas reveal vascular fibrosis. E, NADPH oxidase 2 (Nox2) mRNA expression was measured by quantitative reverse transcription polymerase chain reaction in aortic tissue. F, high-performance liquid chromatography (HPLC) was used to detect nitrate (NO₃⁻) in plasma. Representative chromatograms are shown below the quantification bar graph. G and H, Flow cytometry of aortic tissue identified Ly6G⁻Ly6C⁺ inflammatory monocytes and Ly6G⁺Ly6C⁺ neutrophils inside the vascular wall. Representative original plots of Ly6G⁻Ly6C⁺ and Ly6G⁺Ly6C⁺ cells are shown beside the quantification bar graph (for gating strategy, see Figure IV in the online-only Data Supplement). One-way ANOVA and Bonferroni multiple comparison test; N=8–31 (C), 6–8 (E), 4–5 (F), and 5–9 (G and H) animals per group. Data are means±SEM. *P<0.05; **P<0.01; ***P<0.001, ****P<0.0001.