Mechanosensitive cGMP signaling in vascular smooth muscle cells

01/10/2025 to 30/09/2028

cGMP is an important signaling molecule in the cardiovascular system and increasingly targeted by clinically used drugs. We identified a pronounced heterogeneity of cGMP signaling in smooth muscle cells of blood vessels and discovered a mechanosensitive cGMP path¬way (mechano-cGMP) in many but not all of these cells. In this project, we will study the molecular architecture and mode of action of mechano-cGMP as well as its functional and therapeutic relevance in blood pressure regulation and vascular diseases. We hypothesize that the link between mechanical force and cGMP signaling provides a brake mechanism to prevent hypertension.
We will use innovative tools established in our groups to study cGMP signaling heterogeneity in VSMCs at the biochemical, (patho )physiological, and pharmacological level, with a focus on the recently discovered mechano-cGMP pathway. We will visualize and modulate cGMP signals to analyze the operating mode and relevance of mechano-cGMP in VSMCs in vitro and in vivo.