Increased stiffness characterizes the early change in the arterial wall with subclinical
atherosclerosis. Proteins inducing arterial stiffness in diabetes and hypercholesterolaemia
are largely unknown. This study aimed at determining the pattern of protein expression
in stiffening aorta of diabetic and hypercholesterolaemic mice. Male Ins2+/Akita mice
were crossbred with ApoE-/- (Ins2+/Akita : ApoE-/- ) mice. Relative aortic distension
(relD) values were determined by ultrasound analysis and arterial stiffness modulators
by immunoblotting. Compared with age- and sex-matched C57/BL6 control mice, the aortas
of Ins2+/Akita , ApoE-/- and Ins2+/Akita :ApoE-/- mice showed increased aortic stiffness.
The aortas of Ins2+/Akita , ApoE-/- and Ins2+/Akita :ApoE-/- mice showed greater expression
of VCAM-1, collagen type III, NADPH oxidase and iNOS, as well as reduced elastin,
with increased collagen type III-to-elastin ratio. The aorta of Ins2+/Akita and Ins2+/Akita
:ApoE-/- mice showed higher expression of eNOS and cytoskeletal remodelling proteins,
such as F-actin and α-smooth muscle actin, in addition to increased glycosylated aquaporin
(AQP)-1 and transcription factor NFAT5, which control the expression of genes activated
by high glucose-induced hyperosmotic stress. Diabetic and hypercholesterolaemic mice
have increased aortic stiffness. The association of AQP1 and NFAT5 co-expression with
aortic stiffness in diabetes and hypercholesterolaemia may represent a novel molecular
pathway or therapeutic target.
