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  • PDGF regulates guanylate cyclase expression and cGMP signaling in vascular smooth muscle.

PDGF regulates guanylate cyclase expression and cGMP signaling in vascular smooth muscle.

Communications biology (2022-03-05)
Staffan Hildebrand, Mohamed Ibrahim, Andreas Schlitzer, Lars Maegdefessel, Wilhelm Röll, Alexander Pfeifer
摘要

The nitric oxide-cGMP (NO-cGMP) pathway is of outstanding importance for vascular homeostasis and has multiple beneficial effects in vascular disease. Neointimal hyperplasia after vascular injury is caused by increased proliferation and migration of vascular smooth muscle cells (VSMCs). However, the role of NO-cGMP signaling in human VSMCs in this process is still not fully understood. Here, we investigate the interaction between platelet derived growth factor (PDGF)-signaling, one of the major contributors to neointimal hyperplasia, and the cGMP pathway in vascular smooth muscle, focusing on NO-sensitive soluble guanylyl cyclase (sGC). We show that PDGF reduces sGC expression by activating PI3K and Rac1, which in turn alters Notch ligand signaling. These data are corroborated by gene expression analysis in human atheromas, as well as immunohistological analysis of diseased and injured arteries. Collectively, our data identify the crosstalk between PDGF and NO/sGC signaling pathway in human VSMCs as a potential target to tackle neointimal hyperplasia.

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Anti-Guanylyl Cyclase β1 (ER-19) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
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