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Régulation de la prolifération des cellules musculaires lisses vasculaires par l’activation in vivo du récepteur natriurétique de type C
| Content Provider | Semantic Scholar |
|---|---|
| Author | Rahali, Sofiane |
| Copyright Year | 2016 |
| Abstract | Vascular remodeling due to hyper-proliferation of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) is associated with hypertension. We previously showed that in vivo treatment of SHR with natriuretic peptide receptor type C (NPR-C) specific agonist C-ANP4-23 attenuates the hyper-proliferation of VSMC. We undertook the present study to investigate if the antiproliferative effect of C-ANP4-23 treatment is mediated through the inhibition of the over-expression of cell cycle proteins and explore the signaling molecules contributing to this effect. For this study, twoweek-old SHR and age-matched Wistar Kyoto rats (WKY) rats were injected intraperitoneally with CANP4-23 twice per week for 6 weeks and sacrificed at the end of the 9th week. Blood pressure measurements were done by tail cuff method, proliferation of VSMC was determined by thymidine incorporation and MTT assay, and Western blotting was used to measure the levels of proteins. VSMC from SHR exhibited enhanced proliferation as compared to WKY and C-ANP4-23 treatment attenuated the hyper-proliferation to control levels. In addition the overexpression of cyclin D1, cyclin A, cyclin E, cyclin dependent kinase 2 and 4 (cdk2, cdk4), phosphorylated retinoblastoma protein (pRb) and Giα proteins exhibited by VSMC from SHR was attenuated to control levels. Furthermore, the enhanced phosphorylation of ERK1/2, AKT, EGF-R, PDGF-R, IGF-R and c-Src was significantly decreased by CANP4-23 treatment. Moreover, the enhanced levels of superoxide anion (O2), NADPH oxydase activity, and the enhanced expression of NOX4 and P47phox in SHRs were attenuated by C-ANP4–23. These results indicate that in vivo NPR-C activation attenuates the over-expression of cell cycle proteins through the inhibition of the enhanced oxidative stress, c-Src and EGF-R, PDGF-R, IGF-R activation, MAPK signaling and over-expression of Giα proteins resulting in the inhibition of the hyper-proliferation of VSMC from SHR. Thus, it can be suggested that C-ANP4-23 may be used as a therapeutic agent for the treatment of vascular complications associated with hypertension and atherosclerosis. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/16280/RAHALI_SOFIANE_2016_memoire.pdf?isAllowed=y&sequence=2 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
