Cholesterol accumulation by cells in the blood vessel wall or in thrombi associated with blood vessels is the hallmark of the atherosclerotic lesion. Previous work in our laboratory has shown that platelets can medicate cholesterol accumulation in vascular smooth muscle cells. This study shows that when platelets are activated, they release cholesterol. Washed human or rat platelets, activated with the potent platelet agonist thrombin, released 50 nmoles of cholesterol per 3 billion platelets. This amount represents approximately 20 percent of the platelet cholesterol content. The calcium ionophore, A23187 (5 Mum) was as effective as thrombin in stimulating cholesterol release, whereas, collagen (200 Mug/ml, type I) was somewhat less effective. ADP (200 Mum), a less potent platelet agonist, was ineffective in stimulating cholesterol release. The release of cholesterol from activated platelets was relatively slow (less than 90% released within 2 hours) when compared with the rapid release of serotonin (less than 90% released within 5 min) a constituent of dense granules. Release of cholesterol was inhibited by the platelet antagonist forskolin, an agent that elevates platelet cAMP. Release of cholesterol could be dissociated from release of a cytoplasmic marker lactate dehydrogenase suggesting that cholesterol release did not result simply from platelet lysis. These findings suggest that platelets, in addition to their known function of stimulating proliferation of cells, are also a source of cholesterol that may accumulate in cells. Both of these platelet functions are relevant to the pathogenesis of atherosclerosis, a disease in which cell proliferation and cellular accumulation of cholesterol are characteristic.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL002827-04
Application #
3966657
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
United States
Zip Code