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Cys18-Cys137 Disulfide Bond in Mouse Angiotensinogen Does Not Affect AngII-Dependent Functions In Vivo.
- Source :
- Hypertension (0194911X); Apr2015, Vol. 65 Issue 4, p800-805, 6p
- Publication Year :
- 2015
-
Abstract
- Renin cleavage of angiotensinogen (AGT) releases angiotensin I (AngI) in the initial step of producing all angiotensin peptides. It has been suggested recently that redox regulation of a disulfide bond in AGT involving Cys18-Cys137 may be important to its renin cleavage efficiency in vivo. The purpose of this study was to test this prediction in a mouse model by comparing AngII production and AngII-dependent functions in mice expressing wild-type AGT versus a mutated form of AGT lacking the disulfide bond. Wild-type (hepAGT+/+) and hepatocyte-specific AGT-deficient (hepAGT-/-) littermates were developed in an low-density lipoprotein receptor -/- background. hepAGT+/+ mice were injected intraperitoneally with adeno-associated viral (AAV) vector containing a null insert. hepAGT-/- mice were injected with AAV containing a null insert, wild-type AGT or Cys18Ser and Cys137Ser mutated AGT. Two weeks after AAV injection, mice were fed a Western diet for 12 weeks. Administration of AAV containing either form of AGT led to similar plasma AGT concentrations in hepAGT-/- mice. High plasma renin concentrations in hepAGT-/- mice were suppressed equally by both forms of AGT, which were accompanied by comparable increases of plasma AngII concentrations similar to hepAGT+/+ mice. AAV-driven expression of both forms of AGT led to equivalent increases of systolic blood pressure and augmentation of atherosclerotic lesion size in hepAGT-/- mice. These measurements were comparable to systolic blood pressure and atherosclerotic lesions in hepAGT+/+ mice. These data indicate that the Cys18-Cys137 disulfide bond in AGT is dispensable for AngII production and AngII-dependent functions in mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0194911X
- Volume :
- 65
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Hypertension (0194911X)
- Publication Type :
- Academic Journal
- Accession number :
- 102599056
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.115.05166