Fig. 3

Conditionally endothelial SETD7-deficient alleviates endothelial function in db/db mice. Diabetic BKS-DB^{(Lepr) KO/KO} (db/db) mice and BKS-DB^{(Lepr) WT/WT} (WT/WT) were administrated with AAV-shSetd7 or AAV-Ctr by tail-vein injection to specifically knockdown endothelial SETD7. A Representative images of immunofluorescence SETD7-stained thoracic aorta sections isolated from WT/WT and db/db mice received AAV-shSetd7 or AAV-Ctr. Scale bars, 50 μm. B Representative traces of Ach-induced EDRs in aortae from WT/WT and db/db mice received AAV-shSetd7 or AAV-Ctr. C Concentration-response curves of Ach-induced EDRs in aortae from WT/WT and db/db mice received AAV-shSetd7 or AAV-Ctr (n = 6). D The protein expression of eNOS and VEGF-α in aortic tissues of WT/WT and db/db mice received AAV-shSetd7 or AAV-Ctr (n = 4). E Representative images of the new vessel sprouting from the isolated thoracic aortic rings of WT mice received AAV-shSetd7 or AAV-Ctr in the presence and absence of high glucose (HG, 22 mM) for 10 days (n = 3). The new vessel sprouting was photographed and quantitated at 7, and 10 days of culture (40 ×). F Representative images of H&E-stained and fibrinogen-stained retinal cross-sections of WT/WT and db/db mice received AAV-shSetd7 or AAV-Ctr. Scale bars, 50 μm. G Representative images of the capillaries in trypsin-digested retinas and quantification of pericytes to endothelial cells ratio (PE/EC, n = 5). Scale bars, 20 μm. H The mRNA level of Setd7, Vegfa, and Aqp4 in retinas from WT/WT and db/db mice received AAV-shSetd7 or AAV-Ctr. Statistical significances were calculated using (G) one-way ANOVA, (C–E, H) two-way ANOVA, Tukey’s multiple comparisons tests. Data are expressed as the mean ± SEM, statistical analysis revealed a significant difference with ***p < 0.001, ##p < 0.01, ###p < 0.001, ns = not significant