Poster abstracts

Poster number 5 submitted by Mohamed Hessein-Hassona

Vascular Hypertrophy-Associated Hypertension of Profilin1 Transgenic Mouse Model led to Functional Remodeling of Vasculature

Mohamed D.H. Hassona (Radiology and OSBP), Zeinb A. Abouelnaga (Anesthesiology and Dorothy M. Davis Heart & Lung Research Institute), Mohamed M. Awad (Anesthesiology and Dorothy M. Davis Heart & Lung Research Institute), Mazin A Alhaj (Anesthesiology and Dorothy M. Davis Heart & Lung Research Institute), Sergio D Bergese (Anesthesiology and Dorothy M. Davis Heart & Lung Research Institute), Altaf A Wani (Radiology and OSBP)

Abstract:
Hypertrophy is accompanied with hypertension and till now there is no direct approach to assess the response of these hypertrophic blood vessels towards the vasoactive agents which is important for the treatment of hypertension. We have developed a novel transgenic mouse model by over-expressing the cDNA of human profilin 1 in the blood vessels of transgenic mice. Our results showed significant increases in F/G-actin ratio and in the medial thickness in the vasculature of profilin 1 mice (P<0.05). Western blotting confirmed the activation of the hypertrophic signaling in the VSMCs of the mesenteric arteries in profilin 1 mice such as Phospho-ERK1/2 and Phospho JNK (220.3% and 210.4% respectively, P<0.05). There was also increase in ROCK II kinase and Rho-GTPase activities (310.5% and 280.1% respectively, P<0.05). Our results also showed elevation of blood pressure in profilin1 mice starting at age 6 month (~ 25 mmHg, P<0.05). Functional analyses of mesenteric arteries toward the vasoactive drugs were assessed using wire-myograph. The results showed significant increase in the vascular responses of profilin1mesenteric arteries towards phenylephrine and Cytochalasin D, but, significant decrease in response towards sodium nitrite. In conclusion, vascular hypertrophy of blood vessels led to functional remodeling of the mesenteric arteries as demonstrated by changing the responses towards the vocative agent.

Keywords: Profilin 1, wire-myograph