Agonistic antibodies directed at cell surface receptors and cardiovascular disease

Abstract

Antibodies directed at receptors can block or stimulate them. Hallmark example of the latter action is Graves' disease where antibodies directed at the thyroid-stimulating hormone receptor exert an agonistic action. Recently, compelling evidence has been presented regarding agonistic antibodies directed against the alpha-adrenergic receptor, the beta-adrenergic receptors, the angiotensin II AT1 receptor, and the platelet-derived growth factor-alpha receptor. The antibodies could play a pathogenic role in various cardiovascular diseases, including hypertension, cardiomyopathy, pre-eclampsia, acute humoral rejection, and connective tissue disease. The mechanisms that result in the production of these antibodies are unclear, automated assays to determine their presence are beset with technical difficulties, and the therapeutic implications are uncertain. Nevertheless, the signaling phenomena resulting from these antibodies are well established and mechanistic studies are being intensively pursued. The discovery of agonistic antibodies may provide additional therapeutic avenues.