Vascular hypertrophy-associated hypertension of profilin1 transgenic mouse model leads to functional remodeling of peripheral arteries
| Autor: | Zeinb A. Abouelnaga, Mohammad T. Elnakish, Hamdy H. Hassanain, Mohamed D. H. Hassona, Pascal J. Goldschmidt-Clermont, Mazin A. Alhaj, Mohamed M Awad |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Genetically modified mouse medicine.medical_specialty Pathology Nitric Oxide Synthase Type III Physiology Integrin alpha1 Blood Pressure Mice Transgenic Biology Structural remodeling Muscle Smooth Vascular Muscle hypertrophy Mice Phenylephrine Profilins Physiology (medical) Internal medicine medicine Animals Vasoconstrictor Agents Mesenteric arteries rho-Associated Kinases Resistance vessel Integrin beta1 Hypertrophy Mesenteric Arteries Peripheral Disease Models Animal medicine.anatomical_structure Endocrinology Hypertension Signal transduction Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 298:H2112-H2120 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00016.2010 |
| Popis: | Increased mechanical stress/hypertension in the vessel wall triggers the hypertrophic signaling pathway, resulting in structural remodeling of vasculature. Vascular hypertrophy of resistance vessels leads to reduced compliance and elevation of blood pressure. We showed before that increased expression of profilin1 protein in the medial layer of the aorta induces stress fiber formation, triggering the hypertrophic signaling resulting in vascular hypertrophy and, ultimately, hypertension in older mice. Our hypothesis is that profilin1 induced vascular hypertrophy in resistance vessels, which led to elevation of blood pressure, both of which contributed to the modulation of vascular function. Our results showed significant increases in the expression of α1- and β1-integrins (280 ± 6.3 and 325 ± 7.4%, respectively) and the activation of the Rho/Rho-associated kinase (ROCK) II pathway (260 and 350%, respectively, P < 0.05) in profilin1 mesenteric arteries. The activation of Rho/ROCK led to the inhibition of endothelial nitric oxide synthase expression (39 ± 5.4%; P < 0.05) and phosphorylation (35 ± 4.5%; P < 0.05) but also an increase in myosin light chain 20 phosphorylation (372%, P < 0.05). There were also increases in hypertrophic signaling pathways in the mesenteric arteries of profilin1 mice such as phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH2-terminal kinase (312.15 and 232.5%, respectively, P < 0.05). Functional analyses of mesenteric arteries toward the vasoactive drugs were assessed using wire-myograph and showed significant increases in the vascular responses of profilin1 mesenteric arteries toward phenylephrine, but significant decreases in response toward ROCK inhibitor Y-27632, ACh, sodium nitrite, and cytochalasin D. The changes in vascular responses in the mesenteric arteries of profilin1 mice are due to vascular hypertrophy and the elevation of blood pressure in the profilin1 transgenic mice. |
| Databáze: | OpenAIRE |
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