Atherosclerotic plaque growth

Demonstration of a novel circulating anti-prostacyclin receptor antibody

“…Although the inhibition of PGI 2 binding to its high-affinity binding sites on the platelet surface did not result in the impairment of inhibition of platelet aggregation by the prostanoid (10), the inhibition of PGI 2 binding to its high-affinity binding sites in the receptor macromolecule by the antibody led to the failure of the autacoid to inhibit platelet-stimulated thrombin generation. It is well established that not only is thrombin important in blood coagulation, but it also has crucially important effects on the enhancement of arteriosclerosis both directly and indirectly (19)(20)(21)(22)(23)(24). As such, the inhibition of high-affinity binding of PGI 2 on its receptor molecule on the platelet surface may result in the increase of atherogenesis through unregulated, platelet-stimulated thrombin generation rather than in direct thrombogenesis due to uncontrolled platelet aggregation in individuals with SCI per se.…”

Loss of high-affinity prostacyclin receptors in platelets and the lack of prostaglandin-induced inhibition of platelet-stimulated thrombin generation in subjects with spinal cord injury.

“…The enzyme, by activating endothelial cells, also stimulates the attachment of monocytes to the vessel wall, and it has also been implicated in atherosclerotic plaque formation (27). Furthermore, thrombin-generated fibrin degradation products have been shown to enhance atherosclerotic plaque growth through focal smooth cell proliferation (28).…”

Modulation of Cell Proliferation by Fibrin Degradation Products

“…Fibrin deposition as thombus occurs in wounds, and fibrin deposition and lysis are also integral features of chronic inflammation, healing and repair in pathological lesions such as atherosclerosis, and tumours. We have shown previously that fibrin degradation products (FDP), obtained from wound extracts [2], atherosclerotic lesion extracts [3] and clot lysis 141, can stimulate cell proliferation in and in vivo test system the chick chorioallantoic membrane (CAM). Using affmity columns the cell proliferative activity was shown to reside mainly in the fragment E of fibrin [4].…”