Figure 6.

Vascular lesion development in hypertensive Y/T KO (YAP/TAZ [yes-associated protein 1/WW domain containing transcription regulator 1] knockout) mice. A, Timeline representation of osmotic pump implantation and knockout induction. B, Blood pressure measurement just before euthanization of Ctrl (control) and Y/T KO mice using the tail cuff method. C, Representative images of mesenteric arteries from Ctrl and Y/T KO mice after removal of surrounding fat and tissue. Lesions are highlighted with arrows. D, Bright-field and fluorescence images of cryosections of mesenteric arteries isolated from Ctrl (YAP^fl/fl/TAZ^fl/fl Cre-negative ROSA^mT/mG) and Y/T KO Cre reporter mice (YAP^fl/fl/TAZ^fl/fl Cre/ERT2 ROSA^mT/mG) at 9 or 11 d after the first tamoxifen injection. Top and third row: Verhoeff Van Gieson staining to visualize vascular lesions and the different layers of the vessel wall. Second and fourth row: fluorescence images demonstrating Cre recombination event by using ROSA ^mT/mG Cre reporter mice. Upon tamoxifen-induced activation of Myh11-Cre, the Tomato transgene (red) is excised and replaced by the expression of GFP (green fluorescence protein) in smooth muscle. Note that many of the cells of the neointima are positive for GFP, whereas the cells of the thickened adventitia and endothelial cells are negative. DAPI (4′,6-diamidino-2-phenylindole) was used as a nuclear stain. Dashed line represents the internal elastic lamina. E, Verhoeff Van Gieson staining of mesenteric arteries of Y/T KO mice demonstrates sites of degradation of both the external (white arrowheads) and internal (black arrowheads) elastic lamina (D and E; Ctrl+Ang II [angiotensin II], n=3; Y/T KO+Ang II, n=3). All data are presented as mean±SEM. A indicates adventitia; EEL, external elastic lamina; Endo, endothelium; IEL, internal elastic lamina; M, media; MAP, mean arterial pressure; Myh11‚ myosin heavy chain 11; and NI, neointimal.