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Experimental hypercholesterolemia induces apoptosis in the aortic valve
N M Rajamannan1, G Sangiorgi, M Springett
1Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
Background And Aim Of The Study:
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).
Conclusion:
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.
Insights
Experimental hypercholesterolemia increases apoptosis, or programmed cell death, in rabbit aortic valves. These findings suggest apoptosis may contribute to the development of aortic valve disease.
Area of Science:
- Cardiovascular Biology
- Cellular Pathology
Background:
- Aortic valve disease is a leading cause for valve replacement in the U.S.
- Molecular mechanisms underlying aortic valve disease are largely unknown.
- Apoptosis is implicated in degenerative conditions.
Purpose of the Study:
- To investigate the association between experimental hypercholesterolemia and apoptosis in rabbit aortic valves.
- To determine if apoptosis plays a role in the pathogenesis of aortic valve disease.
Main Methods:
- New Zealand White rabbits were fed a 1% cholesterol diet for 12 weeks.
- Aortic valves were analyzed for apoptosis using TdT-mediated dUTP-biotin nick end-labeling (TUNEL) and transmission electron microscopy.
- Apoptotic cell counts were quantified via computed morphometry.
Main Results:
- Hypercholesterolemic rabbits exhibited significantly increased apoptosis in aortic valves compared to controls (0.1% TUNEL-positive cells).
- TUNEL staining was localized to the atherosclerotic layer of affected valves.
- Apoptosis was not detected in control rabbit valves.
Conclusions:
- Experimental hypercholesterolemia leads to increased apoptosis in rabbit aortic valves.
- These findings suggest that apoptosis may be a key mechanism in the development of hypercholesterolemic aortic valve disease.
- Further research into apoptosis's role in valvular degeneration is warranted.