[Pharmacological analysis of integrin function: inhibition of vascular stenosis and identification of a novel antiplatelet substance].
The long-lasting success of PTCA, a common treatment for patients with coronary artery disease, is hampered by acute reocclusion due to thrombus and by late restenosis due to smooth muscle cell (SMC) migration and proliferation. Recently potent antiplatelet agents such as inhibitors of platelet glycoprotein (GP) IIb/IIIa (alpha IIb/beta 3) have become available and are highly effective in humans. We investigated the inhibitory effects of these compounds on vascular stenosis. Administration of an RGD-containing peptide (non-selective alpha IIb/beta 3 antagonist) results in reduction of neointima, but selective alpha IIb/beta 3 antagonists have no effect. This effect is due both to an early event, which could be due to the inhibition of secretion of PDGF from activated platelets with blocked alpha IIb/beta 3, and to a late event, by interference with SMC alpha v/beta 3. Moreover, platelet adhesion via GPIb/V/IX is a trigger for thrombus formation. Inhibition of platelet adhesion results in the prevention of thrombus formation and the suppression of neointima. However, this effect was supported by the reduction of SMC proliferation. Therefore, these dual inhibitions markedly reduced vascular stenosis. Finally some low molecular mass heat shock proteins (HSPs) appear to act as molecular chaperones, but their physiological roles have not been fully elucidated. We have investigated the physiological role of p20, a kind of HSP, on platelet function. p20 inhibited platelet aggregation. Our findings may provide the basis for a novel defensive system against thrombus formation.
Matsuno
H
H
Department of Pharmacology, Gifu University, School of Medicine, Japan.
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D001808:Blood Vessels / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement; D003251:Constriction, Pathologic / Q000209:etiology / Q000473:pathology; D006801:Humans; D039661:Integrin beta3; D009124:Muscle Proteins / Q000494:pharmacology / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*
D015703:Antigens, CD; D039661:Integrin beta3; D009124:Muscle Proteins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D001312:Aurintricarboxylic Acid