Section Review—Cardiovascular & Renal: Integrins and Cardiovascular Disease

Abstract

Both platelets and neutrophils play major roles in the pathology of ischaemic heart disease. Platelets are involved in the development of an occlusive thrombus, while neutrophils are implicated in the oxidative damage of reperfusion injury. In both cases, integrins play key roles in these pathological processes: in the case of platelets, the fibrinogen receptor glycoprotein (GP) IIb/IIIa; and in the case of neutrophils the β₂ integrins and α_LRI β₃ . In recent years, a number of potent GPIIb/IIIa antagonists have gone into clinical trials. The most advanced of these are monoclonal antibodies and peptide analogues of RGDS. These have shown benefit in preventing reocclusion after thrombolysis and percutaneous transluminal coronary angioplasty (PTCA), as well as in the treatment of unstable angina. A number of non-peptide intravenous and oral preparations are in early clinical trials. At present, there are no suitable antagonists for the β₂ integrins, and these will be an interesting target for future drug discovery.