Angiotensinogen T235 expression is elevated in decidual spiral arteries.

Morgan, Terry K.; Craven, Catherine; Nelson, Lesa; Lalouel, J.-M.; Ward, Kenneth

doi:10.1172/jci119661

Cited by 108 publications

(64 citation statements)

References 47 publications

(51 reference statements)

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“…The protein in plasma is readily cleaved by human renin, resulting in the acute pressor response which could be easily detected by changes in blood pressure. We also showed that we are capable of detecting relatively small differences in expression levels of both RNA and protein, comparable with the proposed differences among Ϫ6G/235Met and Ϫ6A/235Thr alleles (31). This model should, therefore, be suitable in the analysis of the most significant human AGT variants described to date.…”

Section: Discussionsupporting

confidence: 80%

Appropriate Tissue- and Cell-specific Expression of a Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream of the HPRT Locus by Homologous Recombination

Cvetkovic

Yang

Williamson

et al. 2000

Journal of Biological Chemistry

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Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this transgenic mouse model is that the human angiotensinogen gene is inserted into the mouse genome as a single copy at a predefined locus and in a specific orientation-a process that can be repeated utilizing other variants of this gene. We establish the validity of this approach by showing that the hAGT hprt mice have normal tissue-and cell-specific expression of the human angiotensinogen gene and normally produce and process the hAGT protein at physiological levels.

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Section: Discussionsupporting

confidence: 80%

Appropriate Tissue- and Cell-specific Expression of a Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream of the HPRT Locus by Homologous Recombination

Cvetkovic

Yang

Williamson

et al. 2000

Journal of Biological Chemistry

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“…This exchange is located distantly from the renin cleavage site, and in vitro renin-mediated AngI generation is kinetically not different for the 235T variant. Currently, a promoter polymorphism at position -6 (G-6A) in strong linkage disequilibrium (-6G-235M; -6A-235T) is a more plausible candidate for differing AGT transcriptions Morgan et al 1997). Many additional polymorphisms, however, have been identified in the AGT gene, including an additional promoter polymorphism at −20.…”

Section: Polymorphisms In the Angiotensinogen Genementioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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“…Furthermore, elevated Ϫ6(A)/235T-AGT expression was shown in decidual spiral arteries of preeclamptic females (Morgan et al 1997), providing a direct link between increased tissue 235T expression and hypertensive disorders.…”

Section: Discussionmentioning

confidence: 91%