The interaction in between caveolin-1 and transforming growth factor beta receptor i on blood-brain barrier integrity in hypertensive animal model

The blood-brain barrier (BBB) is disrupted in both acute and chronic hypertension. Transforming growth factor beta (TGFβ) increases in circulation in hypertensive conditions, however little is known about its possible effects on brain microvessels. We investigated the impact of TGFβ on BBB integrity in hypertension induced by angiotensin II (ANGII) in mice. Hypertensive animals were treated with SB-431542 that inhibits TGFβRI, and dynasore that blocks plasmalemmal vesicle formation. The alterations in the expression of glucose transporter (Glut)-1, claudin-5, caveolin-1, and glial fibrillary acidic protein (GFAP) were evaluated by immunofluorescence method. Alexa Fluor594-labeled bovine serum albumin was used to assess BBB permeability. ANGII increased arterial blood pressure in animals (P<0.01). Increased BBB permeability to albumin-Alexa594 in hypertension was worsened by dynasore but alleviated by SB-431542 (P<0.01). The expression levels of Glut-1 increased in the cerebral cortex in ANGII, while dynasore and SB-431542 treatments in the same condition decreased even under sham values (P<0.01). The expression of Glut-1 in the hippocampus was found to decrease in ANGII, ANGII+dynasore, and ANGII+SB-431542 groups compared to sham animals (P<0.01). Claudin-5 fluorescence intensity increased in ANGII and decreased in ANGII+SB-431542 groups in the hippocampus (P<0.01). Fluorescence intensity of caveolin-1 dramatically increased in ANGII and ANGII+dynasore groups, however severely decreased in the hippocampus in ANGII+SB-431542 group (P<0.01). GFAP fluorescence intensity decreased in the hippocampus in ANGII+dynasore, and ANGII+SB-431542 groups (P<0.01). Our study suggests that TGFβ signaling could play an important role in BBB integrity owing to our observations of decreased BBB permeability by SB-431542 under hypertensive conditions.