GRAF3 serves as a blood volume-sensitive rheostat to control smooth muscle contractility and blood pressure
| Autor: | Masao Kakoki, Joan M. Taylor, Oliver Smithies, Xue Bai, Kevin D. Mangum, Christopher P. Mack |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Contraction (grammar) RHOA Regulator Blood Pressure Mice Transgenic Blood volume Biology Biochemistry Muscle Smooth Vascular Mice 03 medical and health sciences Gene expression medicine Animals Humans Cells Cultured Blood Volume Brief Report GTPase-Activating Proteins Cell Biology Smooth muscle contraction Phenotype Cell biology 030104 developmental biology medicine.anatomical_structure cardiovascular system Vascular resistance biology.protein |
| Zdroj: | Small GTPases |
| ISSN: | 2154-1256 2154-1248 |
| Popis: | Vascular resistance is a major determinant of BP and is controlled, in large part, by RhoA-dependent smooth muscle cell (SMC) contraction within small peripheral arterioles and previous studies from our lab indicate that GRAF3 is a critical regulator of RhoA in vascular SMC. The elevated contractile responses we observed in GRAF3 deficient vessels coupled with the hypertensive phenotype provided a mechanistic link for the hypertensive locus recently identified within the GRAF3 gene. On the basis of our previous findings that the RhoA signaling axis also controls SMC contractile gene expression and that GRAF3 expression was itself controlled by this pathway, we postulated that GRAF3 serves as an important counter-regulator of SMC phenotype. Indeed, our new findings presented herein indicate that GRAF3 expression acts as a pressure-sensitive rheostat to control vessel tone by both reducing calcium sensitivity and restraining expression of the SMC-specific contractile proteins that support this function. Collectively, these studies highlight the potential therapeutic value of GRAF3 in the control of human hypertension. |
| Databáze: | OpenAIRE |
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