Experimental hypercholesterolemia induces apoptosis in the aortic valve.
OBJECTIVE
Aortic valve disease is presently the number one indication for valve replacement in the United States, yet its molecular mechanisms remain unknown. As apoptosis (programmed cell death) occurs in degenerative disease states, it was postulated that experimental hypercholesterolemia is associated with apoptosis in rabbit aortic valves.


METHODS
New Zealand White rabbits (n = 8) were fed a 1% cholesterol diet for 12 weeks; control rabbits (n = 8) were fed a normal diet. After sacrifice of the animals, the aortic valves were dissected. Apoptosis was identified in the valvular lesion by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique, and confirmed with transmission electron microscopy. The number of apoptotic cells was measured by computed morphometry.


RESULTS
Valves from hypercholesterolemic rabbits showed an increase in apoptosis. TUNEL staining was identified in the atherosclerotic layer of hypercholesterolemic valves (0.1% of cells), but not in the cells of controls (p <0.0001).


CONCLUSIONS
Apoptosis is increased in rabbit aortic valves during experimental hypercholesterolemia. If fatal cellular degeneration occurs in hypercholesterolemic valve disease, these data suggest that apoptosis may play a role in the mechanism of valvular disease.
Rajamannan
N M
NM
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
Sangiorgi
G
G
Springett
M
M
Arnold
K
K
Mohacsi
T
T
Spagnoli
L G
LG
Edwards
W D
WD
Tajik
A J
AJ
Schwartz
R S
RS
D000818:Animals; D001021:Aortic Valve / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D017209:Apoptosis / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D006349:Heart Valve Diseases / Q000473:pathology / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits
D002784:Cholesterol