Nitric oxide and platelet aggregation.

Platelets are small cells, 1/14th the volume of erythrocytes, and about 1000 billion circulate in human blood as smooth anucleate disks. Their job is to survey the lining of our blood vessels, the endothelium. In acute damage and extravasation, platelets are activated by contact with exposed collagen and aggregate together at the wound sites to initiate clotting and stop bleeding. Forming a physical plug to seal a hemorrhaging vessel is the key role of blood platelets. However, milder injury to the endothelium, perhaps a result of high blood pressure, raised plasma cholesterol, or smoking, also causes platelets to adhere to the internal walls of arteries. Such precipitate adhesion and activation of platelets initiates an inflammatory response of the vessel wall and predisposes to vascular complications, including thrombosis, premature heart disease, myocardial infarcts or strokes, and diabetes. It is essential, therefore, that during normal vascular hemostasis platelet activation is tightly controlled. Indeed, both platelets and endothelial cells produce and secrete chemicals that directly inhibit platelet aggregation. A key agent is the free radical gas nitric oxide (NO). Here, we review how this 30-Da molecular messenger is synthesized by a catalytic cassette 10,000 times larger and how it functions to suppress platelet "stickiness." We also present new evidence that directly links plasma lipoproteins with platelet activation: we describe at the molecular level how apoE, a protein with a prominent role in cholesterol transport, interacts with the platelet surface to stimulate NO production and hence attenuate platelet activation.