The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity
J. Clin. Invest. Yuka Ichikawa-Shindo, et al. 118:29 doi:10.1172/JCI33022 [
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Figure 3Abnormalities of vascular structure and gene expression in
RAMP2–/– embryos. (
A–
H) Vascular structure of WT and
RAMP2–/– embryos. Transmission electron micrographs of vitelline arteries (
A and
B), hepatic vessels (
C and
D), and aortas (
E and
F) from E12.5
RAMP2–/– and WT embryos. The vitelline arteries and hepatic vessels from
RAMP2–/– mice showed the detachment of ECs (E) from basement membrane (arrows,
B and
D). In aortas from
RAMP2–/– mice, the smooth muscle cell layer was thinner and rougher than in aortas from WT mice (double-headed arrows,
E and
F). (
G and
H) Immunohistochemical staining for type IV collagen and actin in aortas from WT and
RAMP2–/– mice. Green, immunohistochemical staining using anti–mouse type IV collagen antibody; red, phalloidin (actin); blue, DAPI (nuclei). The structure of the smooth muscle cell layer and the basement membrane showed severe deformity in
RAMP2–/– mice. (
I) Quantitative real-time PCR analysis of gene expression in the umbilical artery from E13.5 embryos. Expression levels are shown relative to the level in WT embryos. VE-cadherin, CDN5, and α2 type IV collagen (COL4A2) expression was reduced in arteries from
RAMP2–/– mice.
n = 6 per group. *
P < 0.05, **
P < 0.01 vs. WT. Scale bars: 2 μm (
A–
D); 25 μm (
E–
H).