Loading...
Please wait, while we are loading the content...
Similar Documents
Modulation des voies de signalisation de l'Ang II par des activateurs du récepteur des proliférateurs de peroxysomes [gamma] dans l'hypertension artérielle
| Content Provider | Semantic Scholar |
|---|---|
| Author | Benkirane, Karim |
| Copyright Year | 2006 |
| Abstract | Angiotensin (Ang) II is implicated in hypertension, vascular remodeling, vascular and cardiac inflammation, and insulin resistance. PPARy activators, thiazolidinediones (TZD), such as rosiglitazone and pioglitazone, can increase insulin sensitivity and improve Ang II-induced vascular inflammation and remodeling. The aims of this thesis are 1) to evaluate the in vitro and in vivo effects of PPARy activators on Ang II-induced signaling pathways (PT3K and MAPK) and celi growth; 2) to investigate the long-term effects of pioglitazone on cardiac inflammation in stroke-prone spontaneously hypertensive rats (SHRSP). My in vitro studies showed that vascular smooth muscle celis (VSMC) derived from rat mesenteric arteries treated with PPARy activators (prostaglandin J2 and rosiglitazone) for 24 hours, inhibited Ang ll-induced PI3K and MAPK signaling pathways through Ang II type 1 (AT1) receptor dependant manner. This was associated with decreased Ang II induced DNA and protein synthesis. PPARy activation also reduced Ang TT-induced growth associated with inhibition ofERK 1/2, Akt/PKB, 4E-BP1, and SHJP2. In vivo, we evaluated the effects of the PPARy activator rosiglitazone on Ang II signaling in aorta and mesenteric arteries. Blood pressure rise in Ang ll-infused rats was attenuated by rosiglitazone. Ang II significantly increased AT1 expression in the mesenteric arteries whereas that of the aorta was decreased, changes which were reversed by rosiglitazone. Akt/PKB activity was increased by Ang II and returned to basal levels under rosiglitazone in both vascular beds. However, Ang II-induced ERK 1/2 activity increased in aorta but not in mesenteric vessels, where 4E-BP1 activity was significantly increased by Ang II and inhibited by PPARy activation. In response to Ang II, SHIP2 activity was increased in both |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/15228/Benkirane_Karim_2006_these.pdf?isAllowed=y&sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
