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- W4315702904 abstract "Background: Pulmonary hypertension (PH) is a disease with a poor prognosis despite the development of various treatments, and a further therapeutic agent is required. C-type natriuretic peptide (CNP), one of the natriuretic peptide family, affects vasorelaxation and inhibition of vascular remodeling through its receptor guanylyl cyclase-B (GC-B). However, the beneficial effect of CNP on PH is still controversial. In this study, we examined the role of the CNP-GC-B pathway in the pathogenesis of PH. Methods and Results: To clarify the effect of the endogenous CNP-GC-B system on PH, we evaluated two types of PH models (monocrotaline pyrrole-induced and hypoxia-induced PH models) by using endothelial cell-specific CNP knockout mice (ecCNP-cKO), endothelial cell-specific GC-B knockout mice (ecGC-B-cKO), and smooth muscle cell-specific CG-B knockout mice (smGC-B-cKO). In both PH models, ecGC-B-cKO and ecCNP-cKO mice exacerbated PH compared to control cre-mice. Besides, mRNA levels of Edn1, IL6 and Ccl2 of the lung were significantly increased in the PH models of these mice. However, PH models of smGC-B-cKO mice showed no significant difference compared to those of control cre-mice. In cultured pulmonary arterial endothelial cells, synthesised CNP significantly attenuated PDGF- or hypoxia-induced increase in mRNA expression of Edn1, IL-6, and Ccl2. Moreover, continuous subcutaneous administration of synthesised CNP by osmotic mini-pump significantly ameliorated PH in PH model mice. Conclusion: CNP plays a protective role in the development of PH via endothelial GC-B through inhibiting endothelin-1 and inflammatory signals involvement. These data suggest CNP could be a novel therapeutic agent for PH." @default.
- W4315702904 created "2023-01-12" @default.
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- W4315702904 date "2023-01-01" @default.
- W4315702904 modified "2023-10-02" @default.
- W4315702904 title "PS-BPB09-7: ENDOTHELIAL CNP-GC-B SYSTEM PLAYS A PROTECTIVE ROLE IN THE DEVELOPMENT OF PULMONARY HYPERTENSION" @default.
- W4315702904 doi "https://doi.org/10.1097/01.hjh.0000915672.90538.a3" @default.
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