Fig. 2

Concept of the HALT & REVERSE project. In the normal heart Protein Quality Control (PQC) and the Heat Shock Response (HSR, upper panel: green area) maintain proteostasis in times of stress. However, with the duration of AF and with increasing age, the heat shock protein (HSP) levels get exhausted. This leads to a derailment of proteostasis (upper panel: red area), resulting in structural remodeling and contractile dysfunction of cardiomyocytes, because of, amongst others, degradation of sarcomers (myolysis, left and right lower panel). AF progresses in time (upper panel: solid line), which is rooted in the underlying electropathology. By pharmacological boosting of HSPs, we aim to HALT or even REVERSE atrial electropathology and consequently AF progression (upper panel: dashed line)