Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis
Abstract A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, an...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55687-9 |
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| author | Moritz Lehners Hannes Schmidt Maria T. K. Zaldivia Daniel Stehle Michael Krämer Andreas Peter Julia Adler Robert Lukowski Susanne Feil Robert Feil |
| author_facet | Moritz Lehners Hannes Schmidt Maria T. K. Zaldivia Daniel Stehle Michael Krämer Andreas Peter Julia Adler Robert Lukowski Susanne Feil Robert Feil |
| author_sort | Moritz Lehners |
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| description | Abstract A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions. Correlative profiling of pathway activity and VSMC phenotype at the single-cell level shows that phenotypic modulation of contractile VSMCs to chondrocyte-like plaque cells during atherogenesis is associated with a switch from ANP/GC‑A to CNP/GC‑B signaling. Silencing of the CNP/GC-B axis in VSMCs results in an increase of chondrocyte-like plaque cells. These findings indicate that the CNP/GC-B/cGMP pathway is a marker and atheroprotective regulator of modulated VSMCs, limiting their transition to chondrocyte-like cells. Overall, this study highlights the plasticity of cGMP signaling in VSMCs and suggests analogies between CNP-dependent remodeling of bone and blood vessels. |
| format | Article |
| id | doaj-art-30244e729d5d4c7ea5b10a920552ae85 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-30244e729d5d4c7ea5b10a920552ae852025-01-19T12:29:50ZengNature PortfolioNature Communications2041-17232025-01-0116112110.1038/s41467-024-55687-9Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosisMoritz Lehners0Hannes Schmidt1Maria T. K. Zaldivia2Daniel Stehle3Michael Krämer4Andreas Peter5Julia Adler6Robert Lukowski7Susanne Feil8Robert Feil9Interfakultäres Institut für Biochemie, University of TübingenInterfakultäres Institut für Biochemie, University of TübingenInterfakultäres Institut für Biochemie, University of TübingenInterfakultäres Institut für Biochemie, University of TübingenInterfakultäres Institut für Biochemie, University of TübingenDepartment for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital TübingenDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of TübingenDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of TübingenInterfakultäres Institut für Biochemie, University of TübingenInterfakultäres Institut für Biochemie, University of TübingenAbstract A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions. Correlative profiling of pathway activity and VSMC phenotype at the single-cell level shows that phenotypic modulation of contractile VSMCs to chondrocyte-like plaque cells during atherogenesis is associated with a switch from ANP/GC‑A to CNP/GC‑B signaling. Silencing of the CNP/GC-B axis in VSMCs results in an increase of chondrocyte-like plaque cells. These findings indicate that the CNP/GC-B/cGMP pathway is a marker and atheroprotective regulator of modulated VSMCs, limiting their transition to chondrocyte-like cells. Overall, this study highlights the plasticity of cGMP signaling in VSMCs and suggests analogies between CNP-dependent remodeling of bone and blood vessels.https://doi.org/10.1038/s41467-024-55687-9 |
| spellingShingle | Moritz Lehners Hannes Schmidt Maria T. K. Zaldivia Daniel Stehle Michael Krämer Andreas Peter Julia Adler Robert Lukowski Susanne Feil Robert Feil Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis Nature Communications |
| title | Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis |
| title_full | Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis |
| title_fullStr | Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis |
| title_full_unstemmed | Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis |
| title_short | Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis |
| title_sort | single cell analysis identifies the cnp gc b cgmp axis as marker and regulator of modulated vsmcs in atherosclerosis |
| url | https://doi.org/10.1038/s41467-024-55687-9 |
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