1. AIM OF THE STUDY 1.1. Background Progressive interstitial fibrosis parallels pathological remodeling in the failing heart. This is particularly the case in patients with post-inflammatory dilated cardiomyopathy, but is also observed in ischemic and hypertensive heart disease. Both, Angiotensin II (AngII) and Endothelin-1 (ET1) induce the formation of the profibrotic cytokine TGFβ and promote fibrosis. From this point of view, it is not surprising that blocking the Renin-Angiotensin-Aldosterone-System (RAAS) evolved as key strategy to slow heart failure progression. Furthermore, recent data also points to an important role of Angiotensin II signaling in heart failure with preserved ejection fraction. In animal models, blocking the effect of AngII or ET1 reduces fibrotic remodeling following myocardial ischemia or in pulmonal hypertension. In line with these findings, we found no evidence of fibrotic remodeling in AGTR1-/- mice who recovered from acute myocarditis. Nevertheless, RAAS blockade is not efficient enough to completely prevent heart failure progression or even rapid deterioration in subgroups of the affected patients. Only recently, Riemekasten et al demonstrated that auto-antibodies against AGTR1 and ETAR are increased in systemic sclerosis and associated with increased pulmonary hypertension and lung fibrosis (2). Moreover, these auto-antibodies were shown to be functional active and to induce downstream expression of TGFβ -mRNA.