Werner, Franziska and Naruke, Takashi and Suelzenbrueck, Lydia and Schaefer, Sarah and Roesch, Melanie and Voelker, Katharina and Krebes, Lisa and Abesser, Marco and Moellmann, Dorothe and Baba, Hideo A. and Schweda, Frank and Zernecke, Alma and Kuhn, Michaela (2024) Auto/Paracrine C-Type Natriuretic Peptide/Cyclic GMP Signaling Prevents Endothelial Dysfunction. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (14): 7800. ISSN 1661-6596, 1422-0067
Full text not available from this repository.Abstract
Endothelial dysfunction is cause and consequence of cardiovascular diseases. The endothelial hormone C-type natriuretic peptide (CNP) regulates vascular tone and the vascular barrier. Its cGMP-synthesizing guanylyl cyclase-B (GC-B) receptor is expressed in endothelial cells themselves. To characterize the role of endothelial CNP/cGMP signaling, we studied mice with endothelial-selective GC-B deletion. Endothelial EC GC-B KO mice had thicker, stiffer aortae and isolated systolic hypertension. This was associated with increased proinflammatory E-selectin and VCAM-1 expression and impaired nitric oxide bioavailability. Atherosclerosis susceptibility was evaluated in such KO and control littermates on Ldlr (low-density lipoprotein receptor)-deficient background fed a Western diet for 10 weeks. Notably, the plaque areas and heights within the aortic roots were markedly increased in the double EC GC-B/Ldlr KO mice. This was accompanied by enhanced macrophage infiltration and greater necrotic cores, indicating unstable plaques. Finally, we found that EC GC-B KO mice had diminished vascular regeneration after critical hind-limb ischemia. Remarkably, all these genotype-dependent changes were only observed in female and not in male mice. Auto/paracrine endothelial CNP/GC-B/cGMP signaling protects from arterial stiffness, systolic hypertension, and atherosclerosis and improves reparative angiogenesis. Interestingly, our data indicate a sex disparity in the connection of diminished CNP/GC-B activity to endothelial dysfunction.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; ARTERIAL STIFFNESS; BLOOD-PRESSURE; RECEPTOR; PHOSPHORYLATION; HYPERTENSION; INFLAMMATION; STIMULATION; EXPRESSION; SYSTEM; endothelial dysfunction; arterial stiffening; systolic hypertension; atherosclerosis; angiogenesis; C-type natriuretic peptide; cyclic GMP |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jan 2026 08:03 |
| Last Modified: | 28 Jan 2026 08:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64894 |
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