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Platelet function in Watanabe heritable hyperlipidemic rabbits. Decreased sensitivity to thromboxane A2
P L Gross1, M L Rand, D V Barrow
1Department of Biochemistry, University of Toronto, Ontario, Canada.
Arteriosclerosis and Thrombosis : a Journal of Vascular Biology
|May 1, 1991
Summary
Platelets from hyperlipidemic rabbits showed reduced aggregation and secretion responses to collagen and thromboxane A2 (TxA2) mimetics, contrasting with diet-induced hyperlipidemia findings.
Area of Science:
- Cardiovascular Biology
- Hematology
- Lipid Metabolism
Background:
- Hyperlipidemia is a risk factor for cardiovascular disease.
- Platelet function alterations may contribute to hyperlipidemia-related complications.
- Watanabe heritable hyperlipidemic (WHHL) rabbits offer a model for genetic hypercholesterolemia.
Purpose of the Study:
- To investigate platelet characteristics and function in WHHL rabbits.
- To compare platelet responses in genetically hyperlipidemic vs. normocholesterolemic rabbits.
- To determine the impact of hypercholesterolemia on platelet aggregation pathways.
Main Methods:
- Comparison of platelets from WHHL and control rabbits.
- Analysis of platelet count, size, and protein content.
- Assessment of platelet aggregation, serotonin secretion, and thromboxane A2 formation in response to agonists (ADP, collagen, U46619, thrombin).
Main Results:
- Platelets from WHHL rabbits had normal cholesterol:phospholipid ratios.
- Collagen-induced aggregation, serotonin secretion, and TxA2 formation were reduced in WHHL platelets.
- Responses to thromboxane A2 mimetic U46619 were significantly less extensive in aspirin-treated WHHL platelets.
- Thrombin-induced responses were not different between WHHL and control platelets.
- WHHL platelets demonstrated hyposensitivity to aggregation induced by TxA2.
Conclusions:
- Genetically determined hypercholesterolemia in WHHL rabbits leads to specific platelet functional deficits.
- These findings contrast with enhanced platelet responses observed in diet-induced hyperlipidemia.
- WHHL rabbit platelets exhibit hyposensitivity to thromboxane A2, impacting aggregation and secretion pathways.