Angiotensin Receptor-1 Blocker Inhibits Atherosclerotic Changes and Endothelial Disruption of the Aortic Valve in Hypercholesterolemic Rabbits
Kumiko Arishiro, MD*,
Masaaki Hoshiga, MD, PhD*,*,
Nobuyuki Negoro, MD, PhD*,
Denan Jin, MD, PhD ,
Shinji Takai, PhD,
Mizuo Miyazaki, MD, PhD,
Tadashi Ishihara, MD, PhD* and
Toshiaki Hanafusa, MD, PhD*
* First Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
Department of Pharmacology, Osaka Medical College, Takatsuki, Osaka, Japan.
View larger version (90K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1 Olmesartan Inhibits Lesion Formation of the Aortic Valve in Hypercholesterolemic Rabbits
(A) a, d, g = control; b, e, h = hypercholesterolemic; c, f, i = hypercholesterolemic olmesartan treated. a to c = hematoxylin and eosin (H&E) staining; d to f = macrophage (RAM11) staining; g to i = osteopontin staining. Inset in b shows Oil red O staining. Insets in e and h represent positive staining at greater magnification. Arrowheads indicate aortic side of valve leaflet. Bar = 200 µm. Quantitation of Oil red O (B), macrophage (C), and osteopontin (D)-stained areas corrected for total area. A = olmesartan; Ao = aorta; V = vehicle.
|
|
View larger version (95K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Olmesartan Inhibits Up-Regulation of ACE in the Aortic Valve Induced by Dietary Cholesterol
Angiotensin-converting enzyme (ACE) immunostaining (black) in sections of aortic valve from control (A), hypercholesterolemic (B), and hypercholesterolemic olmesartan-treated (C) rabbits. Sections are counterstained with methyl green. Inset in B shows the aorta from the same section. Arrowheads indicate aortic side of the valve leaflet. (D) Quantitation of ACE-stained area corrected for total area. Ao = aorta. Bar = 200 µm.
|
|
View larger version (71K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 Olmesartan Preserves Endothelial Integrity of the Aortic Valve
CD31 immunostaining of aortic valve endothelium from control (A), hypercholesterolemic (B), and hypercholesterolemic olmesartan-treated (C) rabbits. Positive staining is shown as red. Arrowheads indicate aortic side of valve leaflet. (D) Quantitation of CD31-positive circumference corrected for valve surface (on each side of valve). Bar = 200 µm. A = olmesartan; Ao = aorta; C = control; V = vehicle.
|
|
View larger version (81K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4 Olmesartan Restores eNOS Expression in the Aortic Valve
Immunostaining for endothelial nitric oxide synthase (eNOS) in aortic valve from control (A), hypercholesterolemic (B), and hypercholesterolemic olmesartan-treated (C) rabbits. Positive staining is shown as red. Arrowheads indicate aortic side of valve leaflet. (D) Quantitation of eNOS-positive circumference corrected for total valve surface. Ao = aorta. Bar = 200 µm.
|
|
View larger version (91K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5 Olmesartan Decreases the Number of Myofibroblasts in the Aortic Valve
Immunostaining for alpha-smooth muscle actin (black) in sections of aortic valve from control (A), hypercholesterolemic (B), and hypercholesterolemic olmesartan-treated (C) rabbits. Sections are counterstained with methyl green. Arrowheads indicate aortic side of valve leaflet. (D) Quantitation of alpha-smooth muscle-stained area corrected for total area. Ao = aorta. Bar = 200 µm.
|
|
View larger version (20K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6 Olmesartan Diminishes Cbfa-1 mRNA Expression in the Aortic Valve
Real-time reverse transcriptional polymerase chain reaction of core binding factor alpha-1 (Cbfa-1) message from aortic valves performed as detailed in the Methods section (n =12 rabbits per group; *p < 0.05). GAPDH = glyceraldehyde-3-phosphate dehydrogenase; mRNA = messenger ribonucleic acid.
|
|
|
