Pathophysiological role of autoantibodies against G-protein-coupled receptors in the cardiovascular system.
After more than 15 years of intensive research in the field of functional autoantibodies (AAB) directed against G-protein-coupled receptors, there is growing evidence of a causal involvement of AAB in various cardiovascular diseases such as dilated cardiomyopathy, peripartum cardiomyopathy, malignant and essential hypertension, and preeclampsia. It has been indicated that AAB against beta-1 adrenergic receptor, alpha-1 adrenergic receptor, angiotensin-II receptor AT(1) and muscarinic M(2)-receptors undergo agonist-like actions on the corresponding receptor and induce a permanent stimulation of G-protein-coupled signal cascades, which may cause Ca(2+) overload and cardiomyocyte destruction.Furthermore, the present review describes how G-protein-coupled receptor AAB are able to activate transcription factor nuclear factor-kappa B, which may regulate the expression of genes involved in immune and inflammatory responses.
Schulze
Wolfgang
W
Max Delbrück Centre for Molecular Medicine;
Kunze
Rudolf
R
Wallukat
Gerd
G